A list of psychotropic medications

MEDICATION LIST

Herbs and Supplements

Complimentary treatments, herbs, and supplements.

Neuromodulation

Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT), and Biofeedback

Medication Algorithms

Psychopharmacology algorithms for mental disorders

Mother-to-Baby

Information about medications during pregnancy and breastfeeding

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What you need to know about stopping psychotropic medications

What you need to know about stopping psychotropic medications

Most medications for mental disorders require a gradual reduction in dosage over weeks to months. Unfortunately, there aren’t formal recommendations from drug manufacturers about how to do this. Most of the recommendations provided in this post are informed by both clinical experience and discussion among colleagues. 

The withdrawal symptoms associated with stopping psychotropic medications can be unpleasant but are rarely dangerous. That being said, a few medications absolutely require a gradual reduction in dose over time to prevent potentially lethal withdrawal reactions. In general, but not always, medications with longer half-lives are less likely to cause severe withdrawal reactions.

Half-life is the time required for the total amount of drug in the body to be reduced by 50%.

For example, fluoxetine (Prozac) has an active metabolite (norfluoxetine) with a half-life of up to two weeks. This means that once you stop taking fluoxetine, it will take up to two weeks for the amount of norfluoxetine to be reduced by 50%. Because of its long half-life, fluoxetine is less likely to cause a withdrawal reaction.

In fact, fluoxetine is often prescribed to reduce withdrawal symptoms associated with tapering off other antidepressants that have shorter half-lives. 

It is important to remember that each individual will have slightly different needs. The way medications are discontinued should be tailored to each individual. The recommendations provided below are for educational purposes only and should not be considered formal medical advice. Please consult your physician for personal health concerns including how to stop your medication. 

Click a medication category to learn more…

Antidepressants

Antidepressant withdrawal symptoms range in severity, but the mnemonic “FINISH” can help you identify them.

 

The selective serotonin reuptake inhibitors (SSRIs) generally require a daily dose reduction of about 25% every one to two weeks. Of the SSRIs, Paroxetine (Paxil) appears to be the most problematic likely due to its relatively short half-life and lack of active metabolites. 

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) such as venlafaxine (Effexor), duloxetine (Duloxetine), and tricyclic antidepressants (e.g., nortriptyline and amitriptyline) may produce more intense withdrawal symptoms if stopped abruptly. While many case reports suggest that both tricyclic antidepressants (TCAs) and SSRIs produce similar symptoms upon discontinuation, TCAs often have additional symptoms such as parkinsonism and balance/coordination issues.

Antidepressant discontinuation symptoms associated with Monoamine Oxidase Inhibitors (MAOIs) may have the most severe symptoms such as aggressiveness, agitation, catatonia, severe cognitive impairment, myoclonus and psychotic symptoms.

In most cases, symptoms develop within three days of stopping or reducing the dose of antidepressant. 

See below for common symptoms associated with discontinuing different antidepressants

Below are examples of how to taper off specific Antidepressants

Mood Stabilizers

Most traditional mood stabilizers, with the exception of lithium, are anti-seizure medications. Abruptly stopping an anti-seizure medication can not only put you at risk for developing withdrawal seizures but can also induce a manic or hypomanic state. 

Withdrawal symptoms include seizures, myoclonic jerks (jerking movements), muscle twitching, severe anxiety, insomnia, agitation, and upset stomach (i.e., nausea, vomiting, diarrhea).

Lithium is worth extra mention as it must be tapered very slowly. Abruptly stopping lithium has been associated with inducing severe depressive or manic states as well as suicidal thoughts. It is very important NOT to stop lithium abruptly. 

Below are examples of how to taper off specific Mood Stabilizers

Benzodiazepines

Benzodiazepines are also anti-seizure medications but are mainly used for anxiety and to aid with alcohol withdrawal symptoms. These medications are dangerous if stopped abruptly.

Withdrawal symptoms include seizures, myoclonic jerks (jerking movements), muscle twitching, tremors, severe anxiety, sweating, insomnia, tachycardia (fast heart rate), elevated blood pressure, agitation, sensory disturbances, hallucinations, confusion, and upset stomach (i.e., nausea, vomiting, diarrhea).

In general, benzodiazepines that are only taken “as needed” don’t require a taper. That is, if they aren’t taken daily. Daily benzodiazepine use will require a gradual taper. In general, the longer the time taking a benzodiazepine, the slower the taper will need to be. 

Below are examples of how to taper off specific benzodiazepines 

Antipsychotics

Antipsychotic medications are a bit of a misnomer because they are prescribed for more than just psychosis. Antipsychotics are also prescribed for mania, hypomania, depression and anxiety. In general, the more anticholinergic the antipsychotic, the slower the taper needs to be. Quetiapine, Clozapine, and Olanzapine are highly anticholinergic and need to be tapered more slowly than the dopamine partial agonists (e.g., Aripiprazole, Brexpiprazole, and Cariprazine).

If switching to a different antipsychotic, the taper will depend on which medications are being switched. 

Below are examples of how to taper off specific antipsychotics

References

  1. J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill. Arlington, VA, US: American Psychiatric Publishing, Inc.
  2. Stahl, S. M. (2017). Stahl’s essential psychopharmacology: Prescriber’s guide (6th ed.). New York, NY, US: Cambridge University Press.
  3. McCarron, Robert M., et al. Lippincotts Primary Care Psychiatry: for Primary Care Clinicians and Trainees, Medical Specialists, Neurologists, Emergency Medical Professionals, Mental Health Providers, and Trainees. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009.
  4. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  8. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  9. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  10. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  11. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  12. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  13. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
  14. Warner CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006 Aug 1;74(3):449-56. PMID: 16913164.

DISCLAIMER: No formal recommendations have been provided drug manufacturers or organizations. The suggestions provided in this post are based on clinical experience and the references provided below. As stated previously, this post is for educational purposes only. Please always consult your physician for personalized medical advice.

Psychodynamic Therapy

psychodynamic therapy

What is Psychodynamic Psychotherapy?

Psychodynamic psychotherapy is the oldest form of psychological therapy used today. Dynamic Psychotherapy, or Psychodynamic therapy, focuses on how influential forces during early development can shape and mold how we think and relate to ourselves and others. Psychodynamic therapy seeks to understand how each patient’s individual life story and subjective experience contribute to emotional suffering. 
 
Psychodynamic therapy is based on the work of Viennese Neurologist Sigmund Freud, who developed psychoanalysis. Freud was influenced by many prominent Viennese physicians including Josef Breuer, Hippolyte Bernheim (who coined the term Psychotherapy) and Jean Martin-Charcot. Building upon the works of his predecessors and mentors, Sigmund Freud developed a “talking cure” as a cathartic treatment for people suffering from an ailment he termed “psychoneurosis.”
 
Freud and his followers believed psychopathology could result from the sequestering of unwanted feelings and memories from conscious awareness.  The goal of psychoanalysis was to “render the unconscious conscious” or bring the suppressed memories and unconscious feelings, desires, and motives into awareness where they could be integrated with the rest of mental life.
 
To do this, Freud employed a technique termed free association whereby patients would lie on a couch facing away from the psychoanalyst and discuss whatever came to mind. Freud believed unconscious material could be accessed through nonverbal behavior and transference/countertransference patterns as they arise in the relationship between patient and therapist. In addition, he believed dreams were driven by unconscious processes that could be analyzed and interpreted. 
 
Psychodynamic theory views mental life and behavior as the result of compromise between conflicting motives as each of us must make choices in the face of many conflicting wishes, fears, and morals. Psychodynamic theory further postulates that all behavior reflects the mind’s effort to maximize pleasure and satisfaction and minimize anxiety and other distressing feelings. The numerous motivations and conflicts are mostly outside our awareness (unconscious) and so, too, are the defense mechanisms we employ to deal with these conflicts (see defense mechanisms post).

The Importance of Childhood

Psychodynamic theory sees adult psychological life as an extension of the mental life of childhood. Childhood experiences, both positive and negative, influence the developing psyche. Psychodynamic therapists are interested in the enduring experiences of the body and of relationships with caretakers in early life. These early experiences are the building blocks for developing unconscious wishes, fantasies, motivations, and core beliefs in adulthood. An exploration of childhood experiences and relationships can help identify where unconscious psychic conflicts originated. It is important to note that contemporary neuroscience and neurobiology provide substantial evidence for the existence of unconscious processes. 

Goals of Psychotherapy

(1) Resolution of internal conflict

(2) Improvement in the quality of one’s relationships

(3) Increased satisfaction with work

(4) More cohesive sense of self

Typical Structure of Therapy: Patient meets with the therapist 1–2 times/week for 45-50 minute sessions.

Therapy Terms

Free Association: Technique invented by Freud as a replacement for hypnosis as a tool for accessing unconscious material. By noticing apparent gaps in associations, psychoanalysts can pick up resistances and clues to unconscious material.

Resistance: 
Resistance reflects the patient’s use of defenses in the therapy to avoid unpleasant emotions, but also to resist change. Examples include silences, missed appointments, forgetting, refusing medication and/or dismissing other interventions the therapist makes. Resistance is a window into the patient’s past and internal mind and is explored together in therapy.

Transference: 
The unconscious mechanism by which patients experience the doctor as a significant figure from the past and thus feelings from the past are reactivated in the here and now with the therapist. Transference occurs in all relationships, but one aspect of dynamic psychotherapy is that the transference is utilized as a tool with which to understand and ultimately modify past patterns of relationships.

Countertransference: 
The set of feelings evoked in the therapist by the patient. Thought to be a joint creation of feelings induced by the patient via projective identification and unresolved conflicts from the therapist’s past. The therapist must be highly self-aware in order to separate his/her own conflicts from the aspect of countertransference that is useful information about the patient’s internal world.

Therapeutic Alliance: 
The shared positive feelings between therapist and patient, relatively free of transference distortion, which support their pursuit of the goals of the treatment.

Working Through: 
The repetitive interpretation of transference and resistance until it is integrated by the patient. The therapist points out patterns in the patient’s outside relationships and relates it to patterns in the relationship with the therapist and in early relationships. It is thought that by re-experiencing these patterns in the relationship with the therapist, they are gradually modified and reintegrated.

Termination: 
Termination is the final phase of the therapy during which the patient reviews the work of the treatment and prepares for the future. The termination phase is likely to reawaken conflicts that have been explored earlier in the treatment, especially conflicts related to separation and autonomy.

References

Caligor, E, Kernberg OF, Yoeman,s FE,(2007) Handbook for Dynamic Psychotherapy for Higher Level Personality Pathology, American Psychiatric Press, 2007

Gabbard, G.O.(2004) Long-term Psychodynamic Psychotherapy: a basic text. Washington, DC, American Psychiatric Publishing, Inc. 2004

Gabbard, G.O (2005): Psychodynamic Psychiatry in Clinical Practice. 4th Edition. Washington, DC, American Psychiatric Publishing, Inc. 2005.

Luborsky L, Crits-Cristoph P (1990) UnderstandingTransference: The Core Conflictual Relationship Theme Method. New York: Basic Books.

Ferrando J., Stephen et al (2008) Psychiatry in Review. 3rd Edition. Educational Testing and Assessment Systems, Inc.

Vaillant G, Bond M, Vaillant C (1986) An empirically validated hierarchy of defense mechanisms. Archives of General Psychiatry 43: 786–94.

Bordin E (1976) The generalizability of the psychoanalytic concept of the working alliance. Psychotherapy: Theory, Research and Practice 16: 252–60.

Allen J, Fonagy P, Bateman A (2008) Mentalizing in Clinical Practice. Washington, DC: American Psychiatric Association.

Hinshelwood R, Zarate O (2006) Introducing Melanie Klein. London: Icon Books.

Stein S (1999) Bion. In S Stein (ed.) Essentials of Psychotherapy. Oxford: Butterworth-Heinemann.

Phillips A (2007) Winnicott. Harmonsworth: Penguin.

Bowlby J (2005) A Secure Base: Parent–Child Attachment and Healthy Human Development. Hove: Routledge.

Mitchell S, Black M (1995) Freud and Beyond: A History of Modern Psychoanalytic Thought. New York: Basic Books.

Stevens A (2001) Jung: A Very Short Introduction. Oxford: Oxford University Press.

What is Parkinson Disease (PD)?

Parkinson Disease (PD)

In his famous piece, “Essay on the shaking palsy,” James Parkinson described a condition he called “paralysis agitans” and believed the medulla, part of the brainstem, was involved. Based on his observations that individuals with the condition showed little to no cognitive impairment, Parkinson hypothesized that the cerebral cortex, the outer crust of the brain, was not involved.
 
We now know, thanks to Jean Martin Charcot and others who were studying the condition, that Parkinson Disease does involve pathological changes within the cerebral cortex.  55-60 million people are affected with Parkinson Disease worldwide, and this number will continue to climb as life expectancy increases and the world population ages. Idiopathic Parkinson’s Disease, Familial Early Onset PD, and Juvenile Onset PD make up the majority of cases. Women are less likely to develop PD because estrogen may be protective.

The classic motor symptoms of PD

(1) Pill Rolling Tremor. Tremors occur due to rhythmic contractions of opposing muscle groups. In PD, the tremor typically occurs at a frequency of 3-5 muscle contraction cycles per second (Hz). The tremor occurs at rest, usually starts unilaterally in the hands and fingers, and diminishes during voluntary movement and sleep. As the disease progresses, the tremor becomes more prominent, bilateral, and eventually rigidity develops. 

(2) Bradykinesia or hypokinesia (slowed movement). Patients with PD are slow in their movements, have difficulty with fine motor control, and experience problems writing and/or using their hands to play instruments or type on a computer keyboard. Spontaneous movements and associated movements are diminished. When we talk to others, we use facial gestures and hand movements to express our emotions; this requires spontaneous movement. When we walk, we swing our arms and move our legs in a specific way to keep our balance; this requires associated movements. When we feel thirsty while reading this lesson, we may reach for our cup of coffee (or water, or wine); this requires initiation of movement. All of these are affected in patient’s with PD which leads to the classic findings of “masked-like” facial expressions, minimal arm swing/shuffling gait, and delayed initiation of voluntary movement. 

(3) Rigidity (Cogwheel Rigidity). When apposing muscle groups are contracting at the same time or are always in a contracted state, this leads to muscle rigidity. When you try to move the arms of an individual with PD, you will find it difficult. There is a passive resistance to movement similar to the negativism or waxy flexibility seen in catatonia. 

(4) Posture problems. Standing or sitting up straight requires the axial/postural muscles. Patient’s with PD have difficulty maintaining appropriate posture and are seen stooped or hunched over. 

The classic “non-motor” symptoms of PD

(1) Cognitive deficits. About 30% of patients with PD may have an accompanying dementia or other forms of cognitive loss. The cognitive deficits seen in patients with PD are thought to be a result of damage to the cholinergic system (especially the nucleus basalis of Meynert) and buildup of insoluble protein aggregates within cortical and sub-cortical structures. 

(2) Constipation. Likely related to cholinergic dysfunction. 

(3) Olfactory deficits. Diminished sense of smell may occur before motor symptoms.

(4) Autonomic Dysfunction. Disrupted sympathetic innervation to the heart and other important organs may lead to bradycardia and hypotension, urinary retention, postural hypotension, sweating, and drooling. 

(5) Rapid Eye Movement Sleep Behavior Disorder (RBD) and other sleep disturbances. During sleep, patients with PD may “act out” their dreams. REM sleep is normally characterized by muscle paralysis. RBD occurs when paralysis of muscles does not occur, and patients move around while dreaming. Insomnia and other sleep disturbances are common in patients with PD.

(6) Mood and personality changes. Depression, apathy, anxiety, irritability, agitation, and psychosis often occur in patients with PD–likely related to destruction of serotonergic projections from the raphe nucleus, noradrenergic projections from the locus coeruleus, cholinergic neurons, dopaminergic projections from the ventral tegmental area, and glutamatergic/GABAergic neurons. 

The Motor System: A Brief Review

The two main motor tracts that control skeletal muscles for movement originate in the motor cortex of the brain and are called the corticospinal tract (or pyramidal tract) and the corticobulbar tract. The corticospinal tract starts in the motor cortex and many, but not all, of the neuronal fibers cross over (or decussate) at the medullary pyramids to eventually synapse on lower motor neurons in the contralateral anterior horn of the spinal cord. Therefore, the right motor cortex primarily controls the left side of the body. Similarly, the corticobulbar tract originates in the motor cortex and many, but not all, of the neuronal fibers cross over and synapses on lower motor neurons in the brain stem. Therefore, the right motor cortex primarily controls movement of the muscles on the left side of the body.

Descending Motor Pathways

The execution of motor movements involves more than just these two tracts. Information from the cortex and subcortical areas are integrated and processed and eventually transmitted to the motor cortex to execute movement. We call these motor “coordination/integration” pathways in the brain “extra pyramidal” because they occur outside of the traditional corticospinal/corticobulbar (pyramidal) motor tracts. The structures that make up the Extrapyramidal motor system include the Basal Ganglia, the Substantia Nigra (in the midbrain), and the subthalamic nucleus.

Extrapyramidal Motor System

The structures that make up the Extrapyramidal motor system include the Basal Ganglia, the Substantia Nigra (in the midbrain), and the subthalamic nucleus. Basal Ganglia, as discussed in the Anatomy sections, include the caudate nucleus, the putamen nucleus, and the globus pallidus. The caudate nucleus and the putamen nucleus are called the “striatum” or “neostriatum” whereas the three nuclei together are referred to as the “corpus striatum.” The globus pallidus is divided into two parts, the internal and external parts. The substantia nigra (SN) is located in the midbrain and is named after the black pigmented neuronal cell bodies seen on anatomical sections. The SN is divided into two parts, the pars reticulata (SNr) and the pars compacta (SNc)  Neuronal inputs to the striatum come from the motor cortex, substantia nigra pars compacta, the thalamus, and subcortical structures like the dorsal raphe nucleus. Information is processed in the striatum and eventually sent to the thalamic nuclei and back to the motor cortex. But from the striatum to the thalamic nuclei, neurons first synapse at the the globus pallidus internal (GPi) and substantia nigra pars reticulata (SNr). From the GPi/SNr, neuronal signals are sent to the thalamic nuclei. To make things more complicated, some of the neurons from the striatum don’t directly synapse on the GPi/SNr and instead take a detour at the globus pallidus external (GPe) and subthalamic nucleus (STN).

 

The extrapyramidal system and the motor nuclei of the thalamus form a loop that obtains information from the cortex and other areas of the brain, integrates and processes it, and relays it back to the motor cortex to modulate motor activity in the corticospinal and corticobulbar tracts. The diagrams can give you a headache but the simple concept is that stimulation of the direct pathway leads to activation of the motor cortex. On the other hand, stimulation of the indirect pathway decreases activation of the motor cortex (“indirect pathway inhibits”). This occurs through a series of glutamatergic and gabaergic connections. Please note that the diagrams are overly simplistic and do not show many of the other neurotransmitters involved (substance P, opioid peptides, neurokinin, etc). 

Dopamine (DA) modulates this circuit. Stimulation of D1 receptors in the striatum by dopamine stimulates the direct pathway and increases motor cortex activity. Stimulation of D2 receptors in the striatum inhibits the indirect pathway. Therefore, the overall effect of dopamine is to increase activity at the motor cortex. Loss of dopamine input from the SNc (as seen in Parkinson’s Disease) or blockade of dopamine receptors via medications (like antipsychotics) will decrease activity in the motor cortex and cause slowed movements. 

Acetylcholine (ACh) has the opposite effect of DA. Stimulation of M2 receptors in the indirect pathway stimulates the indirect pathway whereas stimulation of M1 receptors in the direct pathway inhibit the direct pathway. This leads to an overall net effect of decreased activity at the motor cortex. Note that ACh interneurons are activated by the glutamate neurons from the motor cortex but are normally under inhibitory control by DA from the nigrostriatal tract. This is why we give anticholinergic medications like benztropine (Cogentin) to help with extrapyramidal symptoms (EPS) and/or the slowed movements associated with Parkinson Disease. 

 

L-Dopa

Dopamine does not readily cross the blood brain barrier. However, its precursor, L-Dopa, does. The mainstay treatment for Parkinson’s disease is “dopamine replacement” with L-Dopa. Because L-Dopa is vulnerable to enzymatic degradation (via monoamine oxidases/MAOs,  Catechol-O-Methyl transferases/COMTs, and aromatic amino acid decarboxylases/AADCs) within the intestine, L-Dopa is often administered with blockers of these enzymes (e.g. carbidopa) to ensure L-dopa reaches the brain. Despite the presence of inhibitors of these enzymes, therapeutic doses of L-Dopa still have some conversion to dopamine and norepinephrine in the periphery. This may explain the side effects seen with L-Dopa treatment.  

Side effects of L-Dopa are thought to result from the conversion of L-Dopa to dopamine, norepinephrine, and/or epinephrine in the periphery. Dopamine in the medulla stimulates the chemoreceptor trigger zone to cause nausea/vomiting and dopamine alters gastrointestinal smooth muscle activity leading to gastrointestinal side effects. The conversion of L-Dopa to norepinephrine in the periphery can lead to sympathetic activation of the heart (tachycardia) and other cardiac arrhythmias. Neuropsychiatric symptoms such as depression, anxiety, agitation, aggression, impulsivity problems (gambling, spending) and psychosis (hallucinations and paranoia) can occur as side effects of L-Dopa treatment.

Neuropsychiatric Symptoms of COVID-19

Neuropsychiatric Symptoms of COVID-19

The COVID-19 pandemic has impacted the physical and mental health of many worldwide. Social isolation, work-life changes, and the socioeconomic effects of the pandemic have fundamentally changed the way many people live.  

By now it is apparent that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19 disease, causes severe respiratory dysfunction (i.e., breathing problems) in a substantial number of individuals with acute infection. In addition to cardiopulmonary issues, there are a variety of acute and chronic neurological and neuropsychiatric sequelae that have been reported. 

Neurological and Psychiatric Sequelae of COVID-19

SARS-CoV-2 virus enters the nervous system through the olfactory (smell) and the circulatory (blood) routes. Active central nervous system (CNS) infection, environmental stress, financial stress, social isolation, loss of independence, and changes in family relational dynamics all contribute directly and indirectly to the neuropsychiatric sequalae of COVD-19 infection. It is important to note that individuals with pre-existing neuropsychiatric disorders are at higher risk for developing neuropsychiatric symptoms.

Neuropsychiatric Symptoms of COVID-19
  • Fatigue
  • Memory problems
  • Concentration problems
  • Insomnia
  • Irritability
  • Apathy
  • Depression
  • Mania, Hypomania
  • Anxiety, Fear, Panic attacks
  • Post-Traumatic Stress
  • Psychosis
  • Obsessive Compulsive Symptoms
  • Suicide
  • Grief, Guilt, Helplessness
Neurological Sequelae of COVID-19
  • Dysgeusia (taste dysfunction)
  • Anosmia (olfactory dysfunction)
  • Dizziness
  • Headache
  • Altered Mentation
  • Delirium
  • Confusion
  • Encephalopathy
  • Cerebrovascular disease
  • Ischemic stroke
  • Cerebral venous thrombosis
  • Hemorrhagic stroke
  • Encephalitis
  • Neuromuscular dysfunction
  • Neuropathy
  • Myoclonus
  • Guillain-Barre Syndrome (GBS)
  • Miller-Fisher variant
  • Seizures
  • Cranial Nerve involvement

Delirium and Altered Mental Status

Delirium 

Delirium describes an acute failure of brain functioning. In this way, delirium is analogous to other acute organ failures such as heart failure, liver failure, or kidney failure.

The term Delirium, from latin Delirare (“deviate from the furrow”), refers to acute alterations in attention, consciousness, and cognition. Altered Mental Status (AMS), Encephalopathy, or Altered level of consciousness (ALOC) are terms used interchangeably with delirium in medical settings.

How Common is Delirium?

Prevalence rates vary depending on age, setting, and study. While there is little consistency in reported prevalence rates across studies, many report rates as high as 70-87% in patients admitted to the Intensive Care Unit (ICU) and 15-53% in elderly patients after surgery. In patients admitted to medical-surgical hospitals, rates may be as high as 10-31%. These prevalence rates highlight how common this disorder is and how important it is to recognize and treat. In fact, the mortality rate of untreated delirium can be as high as 15%!

What are common Signs and Symptoms of Delirium?

The hallmark sign of delirium is an acute or abrupt change, within hours or days, in an individual’s mental status. Typically, consciousness, arousal, and attention fluctuate over time (“wax and wane”) such that individuals may go through periods of apparent lucidity followed by periods of confusion. In addition to changes in consciousness, arousal, and attention, other symptoms often include:
  • Cognitive problems 
  • Memory impairment (usually limited to recent memories and formation of new memories)
  • Disorientation to time and place (but rarely to self)
  • Speech and language problems
  • Perceptual disturbances such as illusions and hallucinations (visual hallucinations are probably more common in delirium than auditory hallucinations)
  • Delusions (fixed, false beliefs such as paranoia)

What is the Pathophysiology of Delirium?

The pathophysiology of delirium remains a mystery. However, delirium is probably a final common pathway with many different causes involving inflammatory mediators (cytokines), hormones, and dysregulation of aminergic, cholinergic, glutamatergic, and GABAergic neurotransmission. It is important to note that delirium is always attributable to a medical or organic cause even if the cause cannot be identified (which is often the case). 

Current theory postulates that delirium results from a combination of predisposing factors and precipitating factors. That is, various factors increase the risk for developing delirium but other factors precipitate the delirious state. Think of delirium as spilling water from a cup. The predisposing factor is a cup full of water and the precipitating factor is someone bumping into you.

Predisposing Factors include

  • History of delirium increases the risk for another episode
  • Advanced age
  • Neurocognitive disorders (Dementia)
  • Depression
  • Any neurological insult (Stroke, Traumatic Brain Injury)
  • Alcohol Abuse
  • History of Delirium Tremens
  • Sensory impairment (especially hearing/vision)
  • Recent surgery (especially neurosurgery, cardiac, and transplant)
  • Intensive Care Unit (ICU) stay
  • Sleep deprivation

 Precipitating Factors include

  • Infections: Urinary tract infections (UTI), Pneumonia, Sepsis, Encephalitis, Meningitis, HIV/AIDS
  • Hypoperfusion/Hypoxia: Significant blood loss/volume loss (bleeding), Heart failure, cardiac arrest, arrhythmia, Cerebrovascular Accident (CVA), Anemia (sickle cell, B12 def, Folate def, Iron def)
  • Metabolic Derangement: Hypoglycemia/Hyperglycemia, Hyponatremia/hypernatremia, Uremia, Hyperammonemia
  • Increased Intracranial Pressure: Cerebral edema, Tumors/Mass lesions, Intracranial Hemorrhage, Hypertensive crisis
  • Seizures
  • Poisons
  • Autoimmune diseases: NMDA Receptor Encephalitis, Lupus Cerebritis
  • Tacrolimus (Posterior Reversible Encephalopathy Syndrome)
  • Opioids/Opiates
  • Barbiturates
  • Antihistamines
  • Anticholinergics
  • Benzodiazepines
  • Lithium toxicity
  • Valproic Acid toxicity
  • Tricyclic Antidepressant (TCA) toxicity
  • Serotonin Syndrome
  • Neuroleptic Malignant Syndrome (NMS)
  • Illicit Drugs: Alcohol intoxication/withdrawal, Wernicke-Korsakoff Syndrome, Inhalant Intoxication, Opioid intoxication/withdrawal, Marijuana Intoxication, Synthetic cannabinoids (K2, Spice), Synthetic Cathinones (bath salts), PCP, LSD, Psilocybin

Who is at highest risk?

  • Elderly (>60 years old)
  • Cognitively Impaired Patients
  • Patients with history of CVA
  • Post-op patients
  • Sensory Impaired patients (blind, deaf)
  • Patients in the Intensive Care Unit (ICU)
  • Patients with multiple medical conditions
  • Patients with sepsis (i.e., blood infections)

How do we screen for delirium?

Screening Tools for high risk patients include the Confusion Assessment Method (CAM), Confusion Assessment Method for the ICU (CAM-ICU), Intensive Care Delirium Screening Checklist, Delirium Rating Scale, Memorial Delirium Assessment Scale, and the Nursing Delirium Screening Scale (NuDESC). 

Delirium can be prevented by using various strategies that reduce an individual’s risk. These prevention strategies include close observation (having someone sit with the patient), frequently reorienting the individual to their location/time/date, and enhancing social interaction by engaging and interacting with the patient as much as possible. It is important to keep visible the time (via a large clock), date, and location in case a patient forgets. Encouraging family to visit can be helpful as familiar faces or familiar items (pictures, blankets, etc) can prevent confusion. 

If sensory impairments are present, these need to be addressed (such as providing hearing aids and glasses). One of the most common mistakes hospitals make is closing the curtains and turning out the lights during the day. It is essential to maintain a consistent sleep/wake cycle by minimizing naps during the day and ensuring adequate sunlight so the patient can easily estimate the time of day. Because sleep deprivation is a common precipitating factor, every effort should be made to minimize the disruption of sleep during the night. Lastly, help the patient maintain adequate nutrition and strongly encourage ambulation and/or physical activity.

How is Delirium Treated?

Delirium is reversible and should be considered a medical emergency. If the cause of the delirium is identifiable, treating the medical cause is considered the primary treatment. While addressing the medical cause, it is important to continue to use the prevention strategies above to minimize any contributing factors. A thorough review of medications may provide insight into the cause of confusion. For example, benzodiazepines, opioids, antihistamines, and anticholinergic medications can cause or exacerbate delirium in older adults.

Behavioral strategies include

  • Correcting any sensory impairments, if present (e.g., providing hearing aids and glasses)
  • Keeping the lights on during the day and lights off at night
  • Maintaining a consistent sleep-wake cycle by minimizing naps during the day and ensuring adequate sunlight so the patient can easily estimate the time of day
  • Minimizing the disruption of sleep during the night (e.g., decrease frequency of vital sign checks)
  • Maintaining adequate nutrition
  • Encouraging ambulation and/or physical activity
  • Keeping the date and time visible in the room
  • Frequently asking the patient where he or she is, their name, the time of day, and the reason for being there

If behavioral strategies are not effective, then medications may be used to prevent harm to the patient and staff. Physical restraints should be considered a last resort for severe agitation and violence. 

Medications include

Antipsychotics 

  • Haloperidol (1mg-5mg PO/IM q6hr PRN)
  • Risperidone (0.5mg-2mg PO BID PRN)
  • Quetiapine (25mg-100mg PO q6hr PRN)
  • Olanzapine (2.5mg-10mg PO/IM q6hr PRN)
  • Ziprasidone (10mg-20mg PO/IM q6hr PRN)

Melatonin Modulators 

  • Ramelteon (8mg PO QHS)
  • Melatonin (3mg-10mg PO QHS)

Acetylcholinesterase Inhibitors

  • Physostigmine
  • Donepezil (5mg PO Daily)

Other Medication Options

  • Clonidine
  • Dexmedetomidine (commonly used in ICU)

References

  1. J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  2. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  3. McCarron, Robert M., et al. Lippincotts Primary Care Psychiatry: for Primary Care Clinicians and Trainees, Medical Specialists, Neurologists, Emergency Medical Professionals, Mental Health Providers, and Trainees. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009.
  4. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  5. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences. Sixth Edition.
  6. Blumenfeld, Hal. Neuroanatomy Through Clinical Cases. 2nd ed. Sunderland, Mass.: Sinauer Associates, 2010.
  7. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  8. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  9. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  10. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  11. Neuroscience, Sixth Edition. Dale Purves, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, Richard D. Mooney, Michael L. Platt, and Leonard E. White. Oxford University Press. 2018.
  12. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  13. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  14. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  15. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  16. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  17. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  18. Stein, Lerer, and Stahl. Essential Evidence-Based Psychopharmacology. Second Edition. 2012.

All About Lithium

All About Lithium

1) What type of drug is lithium?

Lithium is a cation metal first used in the 19th century to treat gout. Circa 1940, John Cade discovered that lithium was effective as a mood stabilizing medication for patients with bipolar mania. It is now called a mood stabilizer. 

2) What is lithium used for?

Lithium is one of the best medications we have in the treatment of bipolar disorder. It is also used as an “add-on” medication to antidepressants in patients with severe depression. Lithium is probably the best for euphoric-type mania and has been shown effective for chronic suicidal thoughts in patients with both unipolar and bipolar depression. 

Lithium has also been shown effective for aggression and violent behaviors in patients with impulse-control disorders. Lastly, lithium has been used successfully in patients with general mood instability in patients with psychotic disorders such as schizoaffective disorder and schizophrenia.

3) For bipolar disorder, is it used for manic episodes, depressive episodes, or both? Is it taken between episodes or just during episodes?

Lithium is used for both manic and depressive episodes as well as between episodes to prevent mania and depression. 

See tables below

 
 
 
 
 

4) How effective is it in treating mood disorders? 

Lithium is one of the most effective medications we have for preventing both mania and depression in patients with bipolar disorder. Some experts would argue that lithium is best for euphoric mania and less effective for patients experiencing “mixed states” or “rapid cycling” bipolar disorder, but this is controversial. 

During an acute manic episode, lithium is often combined with other medications to help stabilize mood. Unfortunately, lithium prescriptions have declined over the past 20 years due to development of atypical antipsychotics and because lithium has a narrow therapeutic index (meaning that the therapeutic range is narrow, and it is easy to become toxic from lithium if not taken appropriately or if mixed with certain medications). 

5) How does lithium work to stabilize mood? 

This is still unclear. However, we do know that lithium has a number of actions. Lithium’s interactions with the brain are complex and include modulating serotonin neurotransmission, modulating signal transduction within neurons, and altering transcription of certain genes that promote growth and neuron viability. Lastly, it appears that lithium alters metabolism of dopamine, norepinephrine, and epinephrine in ways that are still incompletely understood. 

6) How long does it take for lithium to start working? 

Varies depending on the patient but typically within 1-3 weeks.   

7) How often does someone take lithium and what are common doses? 

Patients are instructed to take lithium every day. Doses vary but typically we want patients to be dosed such that blood lithium levels are between 0.6-1.2 meq/L. For the average person, the dose range of lithium can be anywhere from 300mg-1,200mg per day (or higher if patient has severe mania) in divided doses. There are controlled-release formulations of lithium that allow for once per day dosing, which is preferred as there is some evidence that once daily dosing reduces the risk of long-term kidney problems. 

8) Are there any patients who should avoid taking lithium? 

There is no absolute contraindication to lithium therapy. A careful risk-benefit analysis should be conducted for each patient and should take into consideration their medical history. In general, elderly patients and patients with renal impairment are dosed lower due to decreased renal elimination. 

Patients who are pregnant or actively trying should speak with their medical provider about continuing or discontinuing lithium during pregnancy. It is important to know that lithium is not absolutely contraindicated during pregnancy. However, there are risks associated with lithium use during pregnancy and these risks (and potential benefits) should be discussed on an individual basis with a psychiatrist. 

Risks associated with lithium use in childhood are not well established and therefore it is rarely used in children.  

9) Are there any health conditions that prevent someone from taking lithium? 

In general, patients with severe renal problems, certain cardiac arrhythmias, severe seizure disorders, and pregnant patients should try alternative medications before starting lithium. Also, lithium should be discontinued prior to Electroconvulsive Therapy (ECT) due to risk of prolonged seizures during ECT treatment. Lithium has also been shown to worsen symptoms of acne and psoriasis. 

10) What are some common drug interactions people should look out for?

Hydration status, hyponatremia (low sodium levels), hypernatremia (elevated sodium levels), caffeine, theophylline, blood pressure medications (thiazide diuretics, Angiotensin Converting Enzyme Inhibitors, Calcium channel blockers), Non-steroidal anti-inflammatory drugs, Carbamazepine, Phenytoin, Methyldopa, and metronidazole (Flagyl) may alter lithium levels. Lithium in combination with high potency antipsychotics such as haloperidol may cause neurotoxicity. Lithium has also been associated with serotonin toxicity if used in combination with serotonergic medications but this is very rare.  

11) What percentage of lithium uses experience side effects? What are some common side effects?

The exact percentages are not well established. Up to 20% of patients taking lithium (more often women) develop clinical hypothyroidism. About 5% of lithium treated patients develop some form of renal impairment but the clinical significance of this is unclear.

Common side effects: Weight gain, tremors, sedation, dizziness, nausea, polyuria, polydipsia, cognitive problems, diarrhea, alopecia, and hypothyroidism are common side effects. 

Hypothyroidism is a common side effect of lithium treatment

12) When should you reach out to a doctor about worrisome side effects or changing your dosing? 

Any sign of lithium toxicity should prompt patients to seek medical attention. This includes worsening tremors, ataxia (balance/coordination problems), slurred speech, nausea, or confusion. 

Lithium Toxicity

1) What is lithium toxicity and who is most at risk for experiencing it?
Lithium toxicity occurs with blood lithium levels above 1.5mEq/L and/or symptoms of lithium toxicity.

See table below

2) What percentage of bipolar patients experience lithium toxicity?
This question is difficult to answer as the data is mixed. 

3) What is a safe blood level of lithium?
0.6mEq/L – 1.2mEq/L is the therapeutic range

4) What are the symptoms of lithium toxicity? Do these vary based on whether it is acute or chronic?
Nausea, vomiting, ataxia, course tremors, slurred speech, confusion, seizures, diarrhea are all symptoms of lithium toxicity.

5) When should you see a doctor or seek emergency help?
If you feel lethargic, nauseated, vomiting/diarrhea, new tremors, slurring speech, or feeling confused/disoriented.

6) If you think you might be experiencing lithium toxicity what are the first steps you should take to treat it?
First thing to do is immediately contact your health provider, stop/reduce the dose of lithium, and drink plenty of fluids. 

7) How do doctors treat lithium toxicity?
Typically, lithium toxicity is managed by reducing or stopping the medication, administering IV fluids, and close monitoring of cardiac, neurologic, and renal functioning. In severe cases, hemodialysis is used.

8) Are there lasting side effects of lithium toxicity?
Renal impairment (decreased renal functioning), abnormal involuntary movements, and thyroid/parathyroid problems have been associated with chronic lithium treatment. 

References

  • Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  • Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  • Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  • J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  • Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  • Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  • Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  • Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). New York, NY, US: Cambridge University Press.
  • Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  • Charney and Nestler’s Neurobiology of Mental Illness. 5th Ed. Oxford University Press. 2017. 

Does Daylight Savings Cause Depression?

What is seasonal affective depressive disorder and why is it more common after we move our clocks forward and back?

Seasonal affective disorder, or SAD, is a form of depression that most often occurs during the fall and winter months when daylight hours are shortened. SAD is not just “winter blues” as symptoms can significantly interfere with daily functioning.

Symptoms of SAD include feeling very tired, sleeping too much, overeating (cravings for carbohydrate rich foods), feeling sad or depressed, lack of interest or pleasure in previously pleasurable activities, low motivation, acting withdrawn, restlessness, concentration problems, indecisiveness, and, if severe, thoughts of death or suicide.

Generally, SAD is more common among women than men and affects approximately 5 percent of adults in the United States. Symptoms usually improve in the early spring and summer months although a small percentage of individuals experience SAD symptoms during the summertime. Not surprisingly, SAD is more common in people who live further from the equator where daylight hours are much shorter during the winter months.

The prevailing hypothesis for why SAD occurs relates to our internal biological clock, also called our circadian rhythm. Our circadian rhythm directs our sleep-wake cycle, our mood, our appetite, our hormone levels, and other important functions. An abrupt change in daylight hours may perturb our rhythm and cause our brains to be “out-of-tune.” In other words, as the duration of daylight hours changes, people can experience a shift in their internal clocks which interferes with daily routines.

How can the effects of seasonal affective depressive disorder be minimized?

Fortunately, there are effective strategies for alleviating symptoms of SAD. The first thing to do is create a routine and stick to it. Behavioral strategies such as daily exercise, healthy well balanced diet rich in Vitamin D, and a consistent sleep routine are helpful for many people. Humans are creatures of habit, so going to sleep and waking up at the same time each day is crucial to maintain the integrity of our circadian cycles. Talk therapy can also be very helpful.

Many people have benefited from happy lamps or happy lights, which are special lamps that mimic natural sunlight. However, it is important to consult with your physician before trying this as it can make some psychiatric disorders worse. Medications are usually a last resort, but the most studied medication for this indication is the noradrenergic-dopamine reuptake inhibitor, bupropion (Wellbutrin).

If we stopped moving our clocks twice each year, might we see fewer cases of seasonal affective depressive disorder?

Although there are no studies that prove a causal link between daylight savings and depression, there are studies that show associations between daylight savings time transitions and increased incidence of depressive episodes. While it makes sense theoretically, more research is needed. Based upon what we know, it is plausible that eliminating daylight savings would result in fewer cases of seasonal affective disorder.

How To Use a Happy Light

DISCLAIMER: Always consult your physician before trying any treatment. Happy Lights may not be for everyone!

All about Dementia

All about Dementia

Dementia is an umbrella term for progressive disorders of learning and memory. Impairments in memory and other cognitive functions make it difficult for those afflicted to cope adequately with their everyday activities. “Neurocognitive disorder,” orDementia,” are nonspecific terms used interchangeably. In 2015, an estimated 47 million people worldwide suffer from dementia.

Common symptoms of Neurocognitive Disorder (i.e., Dementia) include

  • Memory problems
  • Personality changes
  • Mood changes
  • Language problems
  • Perceptual changes
  • Decision-making problems and other Executive dysfunctions (attention, organization, problem solving, planning)

There are different forms of dementia; these include Alzheimer’s disease, vascular dementia, fronto-temporal dementia, dementia with Lewy Bodies, Parkinson’s disease dementia and Korsakoff’s syndrome. However, Alzheimer’s disease accounts for the majority of cases of dementia. In some of these instances, Alzheimer’s disease may occur together with one or more of the other forms of dementia. Below is a brief overview of the different types of dementia and a detailed account of Alzheimer’s disease, the drugs that are currently available for the treatment of this condition and the possible future pharmacological strategies presently under investigation.

Alzheimer’s Disease (AD)

Alzheimer’s disease (AD) is the most common type of dementia (60-80% of cases) and is considered a “cortical” dementia. That is, individuals with AD have problems in the outer “crust” of the brain called the cerebral cortex. The cerebral cortex has many functions depending upon the area. For example, the parietal cortex has a major role in attending to stimuli in the external and internal environments, the temporal cortex as an important role in the identification of stimuli, and the frontal cortex plays an important role in planning, making rational decisions, and preventing impulsive behaviors. In addition to degeneration of the cerebral cortex, other areas of the brain are also affected in AD. For example, memory loss is associated with atrophy of the hippocampus, a structure within the temporal lobes of the brain. Affective (mood) changes suggest problems within a group of structures that make up the “limbic system.” 

Diagnosis of Alzheimer’s Disease

Neurocognitive Disorder (NCD) due to Alzheimer’s disease is a clinical diagnosis and can be definitively diagnosed only by postmortem (after death) direct visualization of the brain. Neurocognitive disorder due to Alzheimer’s disease usually has a slow onset and symptoms usually progress gradually. 

Signs and Symptoms of Alzheimer’s Disease

Patients and their caregivers may notice that tasks that were relatively easy have become more difficult, particularly more complex cognitive tasks. Anhedonia (loss of enjoyment of previously pleasurable activities) is also common. Anomia or anomic aphasia may be experienced, which is an ability to name familiar objects or people. Additionally, problems with misplacing items or getting lost in familiar places occur with increasing frequency.

As the disease progresses, these issues get worse, and other behavioral and cognitive changes occur. Changes in physiological processes, such as disrupted sleep, incontinence, and difficulty swallowing, are seen.

Psychiatric symptoms such as delusions, hallucinations, depressed mood, and agitation (including violent outbursts) may occur.

Tasks or activities of daily living (ADLs) eventually become difficult, including the ability to prepare food, to choose appropriate clothing, and, particularly, to drive. Additionally, the individual’s ability to recognize danger and to accurately and appropriately judge a situation is diminished. Reading and writing become more difficult, and strategies such as making lists may become less effective.

Verbal communication also suffers as the disease progresses, and language becomes confused, with incorrect word usage and mispronunciation of words. A sense of “self” is commonly lost in those with advancing AD. The loss of personal memories contributes to this. With loss of these functions comes withdrawal from social contact with family and friends. AD will eventually take away completely the ability to use language, interact with or even recognize family or friends, and live independently.

For additional information, visit the Alzheimer’s Association website at www.alz.org.

Pathology of Alzheimer’s Disease

Amyloid Plaques and Neurofibrillary Tangles

FIGURE ABOVE: Pathological changes in the brain with advanced Alzheimer’s disease (AD) The brain of an individual with AD is compared with a healthy brain from an age-matched individual. The brain of the individual with AD shows significant atrophy, narrowing of the gyri, widening of the sulci, and enlargement of the ventricles. (Courtesy of Ann C. McKee, MD, Boston University School of Medicine/VA Boston Healthcare System.)

Amyloid plaques and neurofibrillary tangles are the classic pathological findings in the brain of patients with AD. These plaques and tangles cause degeneration of cells throughout the cortex, especially the frontotemporal association cortex. In addition, up to 45% of neuronal synapses are lost as the disease progresses and likely explains the significant cognitive impairment that develops over time in AD.

Amyloid plaques are the result of the accumulation of the beta amyloid protein (β-amyloid/A-beta [Aβ]) between neurons. Aβ is a protein fragment normally produced by the brain by enzymatic cleavage of amyloid precursor protein (APP). APP undergoes enzymatic cleavage by 𝜷-Secretase and 𝜸-Secretase Enzymes (see figure below) to eventually produce either the 40-amino- acid (Aβ40) or the 42-amino-acid (Aβ42) form of Aβ.

Fragments of APP have important roles in kinase activation, facilitation of gene transcription, cholesterol transport regulation, and pro-inflammatory/antimicrobial activities. Normally, these fragments undergo degradation and removal. However, in the brains of those with AD, these protein fragments, particularly Aβ42, accumulate to form plaques. Several different subtypes of plaques exist. Three common types include:

  1. Senile or neuritic plaque has a core of the amyloid protein surrounded by abnormal dendrites or axons. Microglial cells or reactive astrocytes are found in the periphery of many of these plaques.
  2. Focal diffuse deposits of amyloid with no neurites surrounding the core
  3. A dense core of amyloid without neurites. The plaques are considered the long-term outcome of neuritic plaques after the surrounding axons and dendrites have died. 

Neurofibrillary tangles (NFTs) are fibrous inclusions that are abnormally located in the cytoplasm of neurons. The neurons particularly susceptible to NFTs are pyramidal neurons—those with a pyramid-shaped cell body. The primary component of these tangles is the protein tau, which is a protein associated with microtubules, which are long filaments that help maintain cellular structure and provide a “highway” for axonal transport. As a component of these tangles, the tau is abnormally phosphorylated. Other proteins, including ubiquitin, are also found in NFTs. 

In early stages of the disease, NFTs are found in the entorhinal cortex, with progression to the hippocampus and neocortex as the disease process continues. Additionally, neurons in the basal forebrain cholinergic and monoaminergic systems are susceptible to damage by AD pathological processes.

Below is a PET scan comparing healthy brain and AD-affected brain. One of several new methods for visualizing amyloid plaques in living brains, Pittsburgh compound B (PiB) dye accumulates in the plaques and can be visualized using PET scanning. Presence of these plaques is more common in those individuals with Alzheimer’s or significant cognitive impairment. (From Wolk et al., 2009).

Risk Factors for Alzheimer’s Disease

  • Advancing age
  • Family history of dementia or AD
  • Diabetes
  • Obesity
  • Untreated hypertension
  • High cholesterol
  • Stress
  • Sedentary lifestyle
  • History of head trauma or hypoxic brain injury
  • Depression
  • Bipolar disorder
  • Post-traumatic stress disorder (PTSD)

Genetic Risk Factors

Genetic contributors to AD consist of risk genes and deterministic genes. Deterministic genes are those that can directly cause disease. Three deterministic genes are known to directly cause autosomal dominant Alzheimer’s disease (ADAD):

  1. APP, found on chromosome 21
  2. Presenilin-1 (PS-1) on chromosome 14
  3. Presenilin-2 (PS-2) on chromosome 1

In ADAD, symptom onset is likely to occur before age 60 (it can occur as early as the 30s). Although ADAD is of concern, only about 5% of AD cases are familial.

The risk gene with the greatest influence on disease development is the gene for apolipoprotein E (ApoE). ApoE is normally a component of very-low-density lipoproteins (VLDLs). These lipoproteins remove excess cholesterol from the blood and carry it to the liver for degradation. The presence of the gene for the E4 form of this (APOEe4) increases risk; inheritance of this form from both parents increases risk further and may lead to earlier onset of the disease. 

Down Syndrome and Alzheimer’s Disease

AD is closely linked to trisomy 21 (Down Syndrome). By the age of 30 to 40, most patients with Down syndrome will develop the plaques and tangles that are associated with AD. These changes are nearly universal among patients with Down syndrome who reach this age, and although the severity of plaque and tangle accumulation mimics that found in AD, not all such individuals will develop AD. One of the possibilities for the connection is that patients have three copies of the APP gene, which is located on chromosome 21.

Management of Alzheimer’s Disease

Non-medication interventions are essential, effective, and first-line recommendations in the management of AD.

Non-Medication interventions include

  • Correcting any sensory deficits (e.g., hearing aids, eye glasses)
  • Making sure the home is safe by rearranging anything thatmight cause falls (e.g., rugs, slippery mats, etc.)
  • Providing well balanced meals with appropriate caloric intake and hydration with fluids and electrolytes
  • At least 25-30min per day of very mild physical activity with assistance (walking around the house, going outside for a short walk)
  • Minimizing daytime naps
  • Keeping lights on and window shades open during the day and lights off and window shades closed at night. This will promote appropriate sleep-wake cycles. 
  • Keeping mentally stimulated during the day by doing puzzles, crosswords, coloring, reading, etc.
  • Improving sleep by utilizing sleep hygiene techniques (No bright screens before bedtime, no TV in bed, minimize caffeine, make a consistent sleep schedule and/or routine)
  • Minimizing the use of alcohol and other substances as these can have negative effects on mood and cognition

Medications 

While there are no medications to date that have reliably reversed or prevented AD, there are medications that may slow down progression of the disease.

Cholinesterase Inhibitors
Recall that Alzheimer’s disease is associated with loss of cholinergic (acetylcholine) neurons, which are important in memory formation. Acetylcholine neurotransmission can be enhanced in many ways. Pharmacologically, the most common method is to inhibit the enzyme that breaks down acetylcholine, acetylcholinesterase. It seems reasonable to assume that these medications would only prove beneficial in patients who still have adequate cholinergic activity (you can’t promote a neurotransmitter if no neurotransmitter is there to begin with).

NMDA Receptor Antagonists
As previously mentioned, glutamate is the most abundant neurotransmitter in the human brain and high concentrations can be toxic to neurons. When neurons die, they can release intracellular glutamate into the extracellular environment. The glutamate that is released can act on nearby glutamate receptors located on other neurons. 

When NMDA receptors are over-activated by glutamate, calcium channels within the NMDA receptor open and allow a large influx of calcium into the neuron which then induces apoptosis and neuron cell death via biochemical mechanisms that are beyond this discussion. 

Therefore, NMDA receptor antagonist medications like the noncompetitive NMDA receptor antagonist Memantine (Namenda) have been developed to “protect” neurons from NMDA receptor over activation and destruction. Unfortunately, Memantine has shown mixed results in clinical trials but remains an important medication often co-prescribed with acetylcholinesterase inhibitors.

Future Therapies

A𝛽 Antibodies
Recall that accumulation of A𝛽 amyloid proteins make up the pathological amyloid plaques. Scientists are looking into developing monoclonal antibodies specific for A𝛽 amyloid to tag them and destroy them by our immune systems before they can aggregate.

𝜷-Secretase and 𝜸-Secretase Enzyme Inhibitors
These enzymes are involved in the pathway that leads to amyloid plaques. Inhibiting their activity is being studied as a way to reduce the formation of plaques.

ACh Receptor Agonists
The loss of cholinergic activity in the cortex and hippocampus is a key finding in individuals with Alzheimer disease and explains why acetylcholinesterase inhibitors (AChEIs) make sense as a treatment option. An alternative strategy to the use of AChEIs is the use of ACh receptor agonists instead. The use of mACh receptor agonists, such as cevimeline and talsaclidine, while effective in animal models of AD, were not effective in clinical trials at the doses used. ACh also acts on nACh receptors in the hippocampus and cortex. The main subtype of nACh receptor in the brain is the 𝛼7-nicotinic ACh receptor and activation of presynaptic 𝛼7-nicotinic ACh receptors increases the release of ACh from central ACh neurons. A𝛽 is also thought to act as an antagonist at this receptor and this action is blocked by stimulation of 𝛼7-nicotinic ACh receptors. Therefore, 𝛼7-nicotinic ACh receptor agonist drugs may be useful in treating the cognitive deficits in AD.

Other treatments being studied include metal Ion Chelators, antioxidants, and anti-inflammatory agents

Vascular Dementia

Vascular dementia accounts for 20–30% of dementias and often co-occurs with Alzheimer’s Dementia. Vascular dementia can be caused by strokes, heart attacks or any ischemic event that disrupts normal blood flow to (or within) the brain. Impaired blood flow leads to cellular death and damage to brain tissue due to lack of oxygen and nutrients. Symptoms depend on the areas of the brain most affected.

Most common symptoms include

  • Slowed reaction time
  • Poor concentration
  • Poor decision making
  • Confusion
  • Memory impairment
  • Anxiety
  • Hallucinations
  • Ambulation/motor problems 
  • Personality changes

Individuals with vascular dementia usually remain functionally stable for a period of time and then suddenly decline in a step-like manner (see graph below). 

Fronto-Temporal Dementia (FTD)

Fronto-Temporal Dementia (FTD) accounts for 5–10% of patients with dementia and, as the name implies, is characterized by progressive damage to the frontal and temporal lobes. Symptoms depend upon the frontal and temporal cortical areas that are affected, but most patients display the following symptoms:

  1. Changes in personality: Loss of inhibitory behaviors, socially unacceptable behaviors, aggressiveness
  2. Mood changes: Marked lack of empathy with others and mood swings
  3. Language problems: Difficulties in finding the correct word to describe something with prominent circumlocution, which is using many words to try and explain something. Also deficits in spontaneous speech.
  4. Memory problems: Usually memory deficits occur later in the progression of the condition.

FTD is genetically linked in about 30–50% of cases. The gene for tau protein (discussed above) is most commonly affected. The treatment of FTD is symptomatic and supportive. At present, there is no cure or means of slowing down its progression.

Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD)

Dementia with Lewy Bodies (DLB) is also referred to as Lewy Body Dementia and accounts for about 3–5% of dementias. LBD and Parkinson’s Disease Dementia (PDD) are very similar, and both are associated with the presence of Lewy Bodies (LBs) in the brain. Lewy Bodies are abnormal proteins that have aggregated or “clumped” together. These protein aggregates contain the protein 𝛼-synuclein and also play a role in Parkinson’s Disease (PD) with and without dementia. However, patients with DLB do not necessarily have PD, although some patients may have both conditions.

The symptoms of DLB are similar to that of Alzheimer Disease but patients tend to develop attention problems, disordered movements, visuospatial deficits, and visual hallucinations earlier in the course of the illness. Parkinson’s Disease Dementia (PDD) is slightly different than Dementia with Lewy Bodies in that the movement disorder (i.e., slowed movements and pill-rolling tremor) usually presents before the cognitive deficits. Currently there is no cure for DLB or PDD, and the treatment is supportive. However, recent clinical trials have suggested that the drugs used in the treatment of Alzheimer’s disease (acetylcholinesterase inhibitors and glutamate receptor antagonists) may be beneficial in alleviating some of the memory and cognitive problems associated with DLB and PDD. For more information about Parkinson Disease, click here.

Wernicke-Korsakoff Syndrome (WKS)

Korsakoff’s Syndrome (KS) is usually due to a deficiency in thiamine (vitamin B1) that occurs most commonly from malnutrition. Malnutrition due to excessive alcohol intake is the most common cause. Alcohol interferes with the conversion of thiamine into thiamine pyrophosphate, which is its active form. The symptoms of WKS include memory loss, denial that there are any difficulties with memory (lack of insight), problems in acquiring new information and skills, personality changes and inventing convincing stories to fill in gaps in memories (also called confabulation). The lack of thiamine (vitamin B1) causes damage to structures in the brain called mammillary bodies. Mammillary bodies are located in the posterior hypothalamus and are connected to the hippocampus in the medial temporal lobe. Damage to these areas compromise the consolidation of short-term memories into long term memories. Treatment includes withdrawal and abstinence from alcohol and administration of high doses of thiamine. 

References

  1. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  2. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  3. McCarron, Robert M., et al. Lippincotts Primary Care Psychiatry: for Primary Care Clinicians and Trainees, Medical Specialists, Neurologists, Emergency Medical Professionals, Mental Health Providers, and Trainees. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009.
  4. Focus Psychiatry Review, Dsm-5: Dsm-5 Revised Edition by Deborah J. Hales (Author, Editor), Mark Hyman Rapaport (Author, Editor)
  5. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  6. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences.Sixth Edition.
  7. Bear, Mark F.,, Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Fourth edition. Philadelphia: Wolters Kluwer, 2016.
  8. Blumenfeld, Hal. Neuroanatomy Through Clinical Cases. 2nd ed. Sunderland, Mass.: Sinauer Associates, 2010.
  9. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  10. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  11. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  12. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  13. Mendez, M. F., Clark, D. L., Boutros, N. N. (2018). The Brain and Behavior: An Introduction to Behavioral Neuroanatomy. United States: Cambridge University Press.
  14. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  15. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  16. Neuroscience, Sixth Edition. Dale Purves, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, Richard D. Mooney, Michael L. Platt, and Leonard E. White. Oxford University Press. 2018.
  17. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  18. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  19. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  20. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  21. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  22. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  23. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  24. Stein, Lerer, and Stahl. Essential Evidence-Based Psychopharmacology. Second Edition. 2012.
  25. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  26. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.

What do my genetic testing results mean?

What do my genetic testing results mean?

To understand what your Genetic Testing results mean, we have to first review a few concepts.

What are Genes?

Genes are little pieces of DNA that contain the code, or “recipe,” for producing receptors, enzymes, and other important proteins in our bodies.

How an individual responds to a medication will depend primarily on two factors

  1. The quantity and/or “quality” of receptors – this is called pharmacodynamics
  2. How efficiently (or not efficiently) the drug is metabolized (or broken down) and eliminated from the body – this is called pharmacokinetics

Pharmacokinetic Genes code for enzymes that metabolize (or break down) and eliminate medications from the body

After swallowing a medication, it travels to the stomach and intestines where it interacts with enzymes called CYP 450 enzymes. Don’t worry about the names.

CYP 450 enzymes are like Pac-Man swimming around gobbling up medications. There are many different types of CYP450 enzymes, and they all metabolize different medications. These “Pac-Man”-like CYP 450 Enzymes have names such as “CYP3A4” or “CYP3A5”. There are many different types such as CYP2D6, CYP2B6, CYP2C8, CYP2C9, CYP1A2, CYP2C19, CYP2A6, CYP2E1…you get the point.

Most psychotropic medications are metabolized by CYP3A4 and CYP2D6. Some of us have a lot of these enzymes and some of us don’t. Genetics determines how much we have and how well they function. This is why two different people will have two different responses to the same medication.

“Slow” or “intermediate” metabolizers have reduced amounts or reduced activity of specific CYP enzymes and therefore metabolize certain medications slowly.

“Ultrarapid” metabolizers have increased amounts or increased activity of specific CYP enzymes and therefore metabolize certain medications quickly. 

Usually (but not always) the more rapidly you metabolize a medication, the higher the dose will need to be to produce a therapeutic response. The slower you metabolize a medication, the lower the dose will need to be and the greater the probability of developing side effects.

The chart that comes with most genetic testing reports lists which medications are metabolized by which CYP enzymes. To learn more about interpreting these charts in your report, click here.

Pharmacodynamic genes refer to genes that encode the receptors that medications target. 

Most medications work by binding to receptors. Genetics play a major role in the quantity and quality of receptors. 

ADRA2A (ALPHA-2A RECEPTOR) GENE: ADRA2A encodes the alpha-2A adrenergic receptor, which is a norepinephrine (adrenergic) receptor. Alpha-2A receptors are highly concentrated in an area of the brain called the prefrontal cortex (PFC). These receptors help regulate norepinephrine and other important neurotransmitters involved in “higher” brain functions such as focus, concentration, and working memory. Changes in the gene for this receptor have been associated with an altered response to certain ADHD medications. Some ADHD medications directly stimulate the alpha-2A adrenergic receptor, while others indirectly impact the activity of this receptor. For more information on ADRA2A Gene, click here.

HLA-A*3101 & HLA-B*1502: The human leukocyte antigen (HLA) proteins are important in our immune responses. Presence of the HLA-A*3101 and HLA-B*1502 genes increase the risk for serious hypersensitivity reactions, systemic symptoms, and skin reactions to medications known to cause such reactions. Lamictal, Depakote, Tegretol, and Trileptal are examples of medications that may cause serious reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), maculopapular eruptions, and Drug Reaction with Eosinophilia. Remember, this isn’t definitive, and it doesn’t mean you will FOR SURE develop a reaction to these medications if you possess these alleles. For more information on HLA-A3101 and HLA-B*1502, click here.

5HTR2A (SEROTONIN 2A RECEPTOR) GENE:
The 5HTR2A gene codes for the 5HT2A receptor. The 5HT2A receptor is a type of serotonin receptor and important regulator of serotonin signaling. It is also involved in regulating dopamine signaling. The 5HT2A receptor is an important target for many antidepressants and antipsychotics. Variations in this gene have been associated with adverse effects to selective serotonin reuptake inhibitors (SSRIs). For more information on 5HTR2A gene, click here.

SEROTONIN TRANSPORTER PROMOTER GENE (SLC6A4 L/S): The serotonin transporter or “serotonin reuptake pump” is what we block with medications like Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs include medications like Paxil, Prozac, Zoloft, Celexa, Luvox, and Lexapro. To produce this important receptor, we have genes called “promoter” genes that essentially “promote” the production of the serotonin transporter. This “promoter” gene, called the SLC6A4 promoter gene has two lengths – Long and Short. The short length has been associated with decreased production of this important Serotonin Transporter which may reduce responsiveness to certain medications such as SSRIs. Essentially, if you possess the “S” allele, it means you may be less likely to respond robustly to classic SSRI antidepressants, may need higher than normal doses to feel a response, and/or may experience more side effects. But it doesn’t mean you won’t respond at all or that using medications like SSRIs will be harmful in any way. Interestingly, a 1996 article stated that the short (S) allele for the promoter gene can partly account for anxiety-related personality traits. For more information on SLC6A4, click here.

Other Genes Tested

CATECHOL-O-METHYL TRANSFERASE (COMT)

The COMT gene encodes catechol-O-methyltransferase, an enzyme that breaks down dopamine (DA) and norepinephrine (NE). Certain variations in the COMT gene have been associated with different levels of COMT activity.

Reduced COMT activity results in less break down of dopamine and norepinephrine and therefore increased levels of these brain chemicals. Note that this gene has not been a reliable marker of medication outcomes is only provided for information purposes. For more information on COMT, click here.

METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) GENE VARIANT:

Folate, also called vitamin B-9 or folic acid, is a B vitamin found mainly in dark green leafy vegetables, beans, peas, nuts, oranges, lemons, bananas, melons and strawberries. Folate has many important roles in red blood cell formation, cell growth, and cell functioning.

L-methylfolate, the active form of folate, is very important in the production of brain chemicals that regulate mood such as dopamine, norepinephrine, and serotonin. The methylenetetrahydrofolate reductase (MTHFR) enzyme (the chef in the figure below) converts folic acid (folate) into L-methylfolate.

Some individuals carry a mutation (or change in the gene) which results in reduced activity of MTHFR. If activity of MTHFR is reduced, then there is also a reduced capacity to create L-methylfolate.

Without enough L-methylfolate, the body may not be able to produce enough serotonin, dopamine, or norepinephrine and this may explain why certain medications that rely on adequate levels of these brain/mood chemicals don’t work that well in some people.

In those individuals with reduced capacity to convert folate to L-methylfolate, supplementation with L-methylfolate may increase production of those important brain/mood chemicals and hypothetically improve the responsiveness to antidepressants and other medications that rely upon the presence of those brain/mood chemicals to work properly. 

For more information on MTHFR, Click Here.

Genetic testing has limitations…

Current genetic testing allows us to take a sample of DNA and look at various genes that may explain why individuals respond uniquely to medications. While genetic testing doesn’t replace clinical decision-making, it can help guide clinicians and patients. However, remember that genetic testing doesn’t tell us if or how you will respond to specific medications. This is because genetic testing results are based upon associations, not causations. Certain genetic factors are more or less associated with, but do not explain, responses to medications. So, we have to be careful how we interpret genetic testing results.

For more information about psychotropics and genetic testing, visit the GeneSight DNA Test for Psychiatric & Depression Medication.

References

  1. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  2. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  3. Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). New York, NY, US: Cambridge University Press.
  4. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  5. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  6. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  7. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  8. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  9. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.

TASK 6: THE VOICES

  • What was your internal dialogue like?
  • What were the voices in your head saying?
  • Were they mean? Were they positive or negative?
  • Describe what you noticed.

TASK 5: THE SOUND

TASK 4: THE SIGHT AND SMELL

TASK 3: THE TASTE

TASK 2: THE TALK

TASK 1: THE WALK