Brain Exercises

Exercise I

Exercise II

Exercise III

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What Makes a Doctor Great?

Humility | Vulnerability | Empathy | Competency

The human body is one of the most complex, dynamic, and well-oiled machines in the known universe. With a warranty of about fifty to sixty years before rust begins to have its way, the human body requires quality fuel, frequent tune-ups, and constant monitoring to maintain the internal balance necessary to function properly. And the most humbling aspects of these human machines are the similarities they share—similarities that allow thousands of doctors like myself to recognize when “normal” becomes abnormal.

One would assume the great doctor knows more, achieves higher marks, and works the hardest–this makes sense. But there is a secret about taking care of human beings–something that too often goes unnoticed in the fast-paced, virtual world we live in. That is, the power of being human is not in what we are, but who we are; because who we are is far more meaningful than the sum of our mechanical parts.

Statistics, outcomes, and awards have their places in measuring a doctor’s performance, but they certainly don’t define the qualities of a human being. Doctors are not gods. And if they’re great, they aren’t robots either. A great doctor tunes in to something fundamental about humans–no matter who you are, where you come from, or what your status is in society, it is encoded in our biology to seek those who validate us, listen to us, understand us, and care about us. 

I like to think of “well-being” as the state in which our minds triumph over our matter—a state in which our soul, smirking at the incompetency and dependency of our organic biomolecules, takes the driver’s seat of our most magnificent vehicle of inanimate carbons to give it meaning and purpose. And it isn’t until the human machine begins to fail that we are humbled by our soul’s inadequacies at handling the physical world–and we begin slowly losing the hope that fuels our motivational energy to keep fighting.

A great doctor has ears like our best friend, the heart of a relative, and the professionalism of a leader—the type who would rather stand side by side and lead together than stand in front and lead alone. These qualities are not something one learns in four years of medical school. They are acquired continuously throughout life, beginning in childhood. Our experiences and interactions with the world constantly influence our souls–molding them into unique entities each with a different story to tell. And the great doctor listens empathically to those stories working diligently to rebuild hope and a sense of control.

Having grown up in a medical family, I’ve encountered many doctors who have this way about them. Their white coat goes on, and somehow the human underneath becomes a figurative Wizard of Oz—an immortal superpower who could do no wrong. The M.D. after their name is a sign not only of their accomplishments, but a marker of their identity. It becomes them. They are the combination of prestige, honor, and respect. They save lives and use sophisticated words and drink Starbucks. They go to meetings to be revered and write papers to be cited. The white coat is not only a way to publicly identify their status within the health system, but it becomes a cloak—a way of covering up the mortal, fatigued, and emotional human being hiding underneath. These types of doctors save many lives, they make a lot of money, and they are well-respected. But whether or not they are great doctors is about something more meaningful than can be described in words. In fact, the value words have in describing a great doctor is about the same the white coat has in identifying one.

It’s the feeling you get from the initial handshake, the way the doctor looks into your eyes rather than at them. It’s the feeling of being understood and feeling important and worthwhile. It’s the feeling of being appreciated as a whole rather than a bullet list of problems. After all, human beings aren’t a list of definitions or an anatomical conglomeration to memorize. We are social beings who need more than just a white coat and M.D. to make us feel something so essential and simple; something that has been wired as part of our evolution before the word “doctor” was even invented.

The healers our patients seek are those who nurture and attend to the wounded souls as they battle the mortality and finality of their physical bodies. And being a great doctor is not about preventing the inevitability of death; it’s about embracing the quality of life. It’s about healing the soul, the driver, the part of us that not only keeps us whole, but gives us the will to continue living and breathing.

That, in my opinion, is what separates the good from the great.

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Serotonin Syndrome or Neuroleptic Malignant Syndrome?

Serotonin Syndrome and Neuroleptic Malignant Syndrome, and Malignant Catatonia are very difficult distinguish clinically. All three syndromes present with some degree of muscle rigidity, unstable vital signs, mental status changes, and sweating. Subtle differences in the presentation of each can help clinicians distinguish and appropriately manage these underrecognized syndromes.

Below we provide a basic review of Serotonin Syndrome and Neuroleptic Malignant Syndrome (NMS). Interestingly, many experts believe NMS to be on a spectrum that includes Malignant Catatonia. Malignant Catatonia, although not discussed here, has a presentation almost identical to NMS. 

Serotonin Syndrome

Serotonin Toxicity, or Serotonin syndrome (SS), is an iatrogenic syndrome. This means it is most commonly caused by medications or medical treatment.

Medications that alter serotonin functioning, especially those that potentiate serotonergic tone, are often implicated in the pathophysiology of this syndrome. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclics (TCAs), and monoamine oxidase inhibitors (MAOIs) are a few examples of medications that can induce serotonin syndrome.

Most cases of serotonin syndrome are mild and self-limited, but severe cases have mortality rates as high as 11%. Serotonin Syndrome is thought to be dependent on excessive stimulation of 5HT1A and 5HT2 receptors. About 15% of overdoses of selective serotonin reuptake inhibitors (SSRIs) result in illness suggestive of serotonin syndrome.

It is important to note that serotonin syndrome may occur when patients taking a monoamine oxidase inhibitor are administered other serotonergic agents such as SSRIs, buspirone or venlafaxine. The same is true for combinations of antidepressants with the mood stabilizer lithium or the antibiotic linezolid. Individuals who are slow metabolizers of serotonin may be particularly susceptible to Serotonin Syndrome. 

Medications Associated with Serotonin Toxicity

  • SSRIs, SNRIs, NDRIs, TCAs
  • Buspirone
  • MOAIs
  • Linezolid
  • Ritonavir
  • Lithium
  • Antiemetic agents: Ondansetron, metoclopramide
  • Triptans
  • Serotonergic antipsychotics

Clinical Features

Patients with serotonin toxicity usually present with rapid onset (within 24 hours) of altered mentation, confusion, stupor, nausea, sweating, and muscle rigidity. Patients are usually nonverbal with significant myoclonus, especially of the lower extremities. Hyperactive lower extremity reflexes, hyperactive bowel sounds, and lower extremity myoclonus are all suggestive of Serotonin toxicity and can help differentiate serotonin syndrome and NMS. The gastrointestinal symptoms associated with serotonin syndrome are likely due to the large amounts of serotonin contained in our guts (more than our brains actually!)

Hyperthermia, diaphoresis (i.e., sweating), and shivering/tremulousness may accompany the above. The patient is often confused, stiff, warm to touch, and mumbling.

Signs of Serotonin Toxicity 

  • Altered Mental Status, Confusion, Coma, Stupor, Irritability, euphoria
  • Hyperreflexia, tremor, myoclonus, ankle clonus
  • Autonomic instability (similar to NMS)
  • Temperature dysregulation (Shivering)
  • Gastrointestinal Symptoms (Nausea/Vomiting/Diarrhea)
  • Elevated CK (relatively uncommon, but can occur)
  • Elevated White Blood Cell Count
  • Elevated Liver Enzymes

To facilitate consistency in diagnosis, and accurately, the Hunter criteria were developed. Essentially, in any patient who has taken a serotonin medication they must also display other signs as listed below to meet criteria for Serotonin Toxicity. 

Hunter Criteria

Treatment of Serotonin Syndrome

The treatment for Serotonin Syndrome is mostly supportive. Monitoring vital signs, oxygenation, hydration status, and blood pressure are essential. Cooling blankets may be used when hyperthermia becomes dangerous. Medications such as benzodiazepines (e.g. Lorazepam/Ativan) can help with tremulousness and muscle rigidity. Cyproheptadine, a serotonin antagonist, can also help hasten recovery. Propranolol is often used to stabilize heart rate and blood pressure. 

Neuroleptic Malignant Syndrome (NMS)

Overview

Neuroleptic Malignant Syndrome (NMS) is most likely caused by first generation antipsychotic medications, especially high-potency agents like haloperidol. NMS is thought to be due, in part, to decreased dopaminergic tone in the basal ganglia. The rapid withdrawal of dopamine agonists or L-dopa may also induce NMS. Some experts consider NMS “Neuroleptic-induced Catatonia,” given the similarities in presentation. The mortality rate for NMS is about 15% in well-managed cases and most individuals require treatment in an intensive care setting. Individuals with preexisting disorders of the basal ganglia (Parkinson Disease, Wilson’s Disease, Huntington Disease, etc.) or history of catatonia are at significant risk for developing NMS. 

Clinical Features of NMS

NMS typically develops over a few days with slow onset of muscle rigidity, blood pressure instability, mental status changes and hyperthermia. When obtaining the patient’s history there is often a recent addition of a dopamine antagonist or a recent withdrawal of a dopamine agonist that likely explains the cause. Electroencephalography (EEG) is abnormal in about 50% of cases and most commonly shows generalized slowing. Creatine Kinase (CK) levels can be elevated up to 10x normal. In most cases, neuroimaging studies and CSF studies are normal. 

Clinical Findings

  • Hyperthermia >100.4F on two occasions
  • Rigidity
  • Mental Status Changes
  • Creatine Kinase (CK) at least 4 x normal
  • Blood Pressure >25% baseline or >20mmHg fluctuation in 24 hours
  • Heart Rate > 25% baseline
  • Respiratory Rate > 50% baseline
  • Negative work up for other causes
  • EEG Abnormal in about 50% of cases: Generalized slowing
  • CT Normal in >90% of cases
  • CSF studies normal in >90% of cases

Treatment

Similar to Serotonin Syndrome, treatment for NMS is supportive. Intravenous fluids, cooling blankets, and benzodiazepines are mainstay treatments. Dantrolene, a ryanodine receptor antagonist and muscle excitation-contraction de-coupler, may be used for muscle rigidity, which is the primary cause of hyperthermia. Bromocriptine, a dopamine agonist, has been helpful in some cases. Severe cases unresponsive to supportive treatment may be successfully treated with electroconvulsive therapy (ECT). Although no formal recommendation exists for when to reintroduce the problematic medication, most of us recommend at least two to four weeks.

Serotonin Syndrome Vs. Neuroleptic Malignant Syndrome (NMS)

References

  1. Oldham, Mark A., and Hochang B. Lee. “Catatonia Vis-à-vis Delirium: The Significance of Recognizing Catatonia in Altered Mental Status.” General Hospital Psychiatry 37.6 (2015): 554-59. Web.
  2. Stern, Theodore A., Gregory L. Fricchione, and Jerrold F. Rosenbaum. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 6th ed. N.p.: n.p., 2010. Print.
  3. Tandon, Rajiv, Stephan Heckers, Juan Bustillo, Deanna M. Barch, Wolfgang Gaebel, Raquel E. Gur, Dolores Malaspina, Michael J. Owen, Susan Schultz, Ming Tsuang, Jim Van Os, and William Carpenter. “Catatonia in DSM-5.” Schizophrenia Research 150.1 (2013): 26-30. Web.
  4. Fink, Max, and Michael Alan Taylor. “Catatonia: A History.” Catatonia (n.d.): 1-18. Web.
  5. Jaimes-AlbornozW, Serra-Mestres J. Prevalence and clinical correlations of catatonia in older adults referred to a liaison psychiatry service in a general hospital. Gen Hosp Psychiatry 2013;35:512–6.
  6. Grover S, Ghosh A, Ghormode D. Do patients of delirium have catatonic features? An exploratory study. Psychiatry Clin Neurosci 2014;68:644–51.
  7. Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review Sher, Yelizaveta et al. Psychosomatics , Volume 56 , Issue 6 , 615 – 625
  8. Catatonia in Medically Ill Patients An Evidence-Based Medicine (EBM) Monograph for Psychosomatic Medicine Practice. Academy of psychosomatic medicine
  9. Levenson, James L. Essentials of Psychosomatic Medicine. Washington, DC: American Psychiatric Pub., 2007. Print.
  10. Kirkhart, Rob et al. “The Detection and Measurement of Catatonia.” Psychiatry (Edgmont) 4.9 (2007): 52–56. Print.
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The Mute Patient

Mr. Jones is a 56 year old husband of three children and a successful CEO. He was brought to the hospital by his wife who was concerned about her husbands change in behavior. “I woke up yesterday and found him lying in bed staring at the ceiling. He wouldn’t make eye contact with me and has spoken only three words in the past 24 hours. Could he have suffered a stroke?” Mr. Jones suffers from bipolar disorder and has been adherent with his medications. He appeared disheveled and has not eaten in over 24 hours.

On examination, Mr. Jones was not responsive. He did not make eye contact but his eyes were open and he appeared awake. His eyes blink to threat (i.e., not blind) and he resists any attempts to move his upper and lower extremities. Neuroimaging of his brain appears normal, electroencephalography (EEG) shows no signs of epileptic foci, and his labs are normal. The astute clinician suggests an intravenous (IV) Lorazepam (Ativan) challenge for suspected Catatonia. After two doses, Mr. Jones begins to respond normally, moves spontaneously, and asks why he was brought to the hospital.

What is Catatonia?

History

Catatonia is a psychomotor disorder whereby affected individuals display abnormal behaviors and movements. Most commonly, there is a reduction in spontaneous movements, social withdrawal, stupor, mutism, stereotyped or repetitive movements, or resistance to others’ attempts to move them.

Although the signs and symptoms of Catatonia have been described in the literature for hundreds of years, it wasn’t until the 1870s that Karl Kahlbaum characterized catatonia as a distinct syndrome. In an effort to establish a nosology for mental disorders, Emil Kraepelin further expanded upon Kahlbaum’s work and classified catatonia, hebephrenia and dementia paranoides as a single entity he termed “dementia praecox” (dementia of the young). Eugen Bleuler (1907), inspired by Kraepelin, adopted the view that catatonia was part of a group of severe idiopathic deteriorating psychoses, which he renamed the “schizophrenias.”

It is important to mention that Kraepelin and Bleuler both recognized catatonic symptoms could emerge from mood disorders, but it wasn’t added as a specifier until many years later. Today, we recognize catatonia as a syndrome associated with psychotic disorders, mood disorders, neurological diseases, toxic-metabolic states, and infections. 

Epidemiology

  • The prevalence of catatonia in acute medical settings is about 1.6-6.3%
  • Incidence of catatonia during acute psychosis is about 7-17%
  • Incidence of catatonia during a mood episode is about 13-31%
  • The cause of catatonia is idiopathic/unknown in about 4-46% of cases

Diagnosis of Catatonia

The diagnosis of Catatonia can be made when three or more of he following symptoms occur together:

  1. Stupor
  2. Catalepsy 
  3. Waxy flexibility 
  4. Mutism
  5. Negativism
  6. Posturing
  7. Mannerism
  8. Stereotypy
  9. Agitation (not influence by external stimuli)
  10. Grimacing
  11. Echolalia 
  12. Echopraxia

In addition, there must be evidence from history, labs, and/or imaging that symptoms are from a medical cause and are not better explained by another mental disorder. Controversially, criterion D in DSM-5 requires that Catatonia not be diagnosed if it occurs exclusively during a delirium period. The controversy exists because Catatonia and Delirium can present simultaneously. A recent study reported a 12-37% incidence of catatonia in patients with delirium.

Below is a photo of a man with catatonia. As you can see, he is posturing–a classic catatonic sign. Some patients may remain in the same position for many hours. Although we typically associate catatonia with this classic sign, in most cases posturing isn’t a prominent sign/symptom.

Screening Tools

The Bush Francis Catatonia Rating Scale (BFCRS) is the most widely used screening tool for Catatonia. Click the link below to view the PDF. 

Bush Francis Catatonia Rating Scale (BFCRS)

Pathophysiology of Catatonia

The pathophysiology of Catatonia remains under investigation. However, dysfunction in numerous brain circuits such as the dopaminergic system, GABAergic system, Cholinergic system, and Glutamatergic system have been demonstrated.  Recall that dopamine is important in value-based decision making in the face of threat. Dopamine also plays a role in motivational and hedonic drive as well as initiation of voluntary movement. A relative decrease in dopamine in numerous brain circuits has been demonstrated in patients with Catatonia. It is worth mentioning that catatonia is thought to be on the same spectrum as Neuroleptic Malignant Syndrome (NMS). 

Brain Circuits Implicated:

Basal ganglia thalamocortical tracts: Rigidity (through motor circuit)

Anterior cingulate-medial orbitofrontal circuit: Akinetic mutism,

Hypothalamic connections: hyperthermia, and autonomic dysfunction

Lateral orbitofrontal circuit: Imitative and repetitive behaviors

Medical Work-Up for Catatonia

Obtain a Thorough History

  • New onset in older adults (>65yo) suggests a medical cause of catatonia rather than primary “psychogenic” catatonia
  • If >2 weeks of symptoms: More likely related to a psychotic disorder or medical illness than mood disorders
  • Acute change? Insidious change?
  • New medications? Medication changes?
  • Illicit Drug use?
  • Previous catatonic episodes?

Review All Medications

The following medications are often overlooked but are known to cause catatonia:

  • Prochlorperazine
  • Linezolid
  • Corticosteroids
  • Disulfiram
  • Ketamine
  • Phencyclidine (PCP)
  • Synthetic Cathinones (“Bath Salts”)
  • Withdrawal from sedative-hypnotics/alcohol (e.g., barbiturates, benzodiazepines, alcohol)
  • Withdrawal from dopaminergic agents (e.g., L-dopa)

Rule Out Mimickers of Catatonia

  • Selective mutism
  • Aphasia
  • Parkinson Disease
  • Malignant hyperthermia
  • Central Pontine Myelinolysis/Locked-in Syndrome
  • Malingering
  • Somatoform illness
  • Dissociative states
  • Failure to thrive in Elderly

Diagnostic Tests

  • Electroencephalography (EEG) is typically normal in catatonia but may show generalized slowing if there is medically-related cause. Brain imaging such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) studies are typically normal if not medically-related. Lumbar Puncture (LP) may be performed to rule out encephalitis or other central nervous system inflammatory, infectious, or autoimmune process.

Treatment of Catatonia

The treatment of the catatonic patient begins with investigating potential underlying causes and treating them appropriately. Be sure to stop any medications that could be contributing to the catatonic state. This includes all antipsychotics. Consider a trial of intravenous lorazepam 2mg and monitor for a response. If no response within 60 minutes, administer a second dose. If still no response, consider adding either a dopamine agonist, memantine, or zolpidem. In cases of malignant catatonia, immediately initiate electroconvulsive therapy (ECT). 

Treatment Steps

  1. Treat underlying medical cause (if any)
  2. Stop contributory medications including all antipsychotics 
  3. Conduct a lorazepam challenge: Lorazepam 2 mg intravenous (IV) in adults | Lorazepam 0.5-1 mg IV in children/elderly
  4. Monitor for improvement in symptoms
  5. If partial or no response after 30 min to one hour, give additional dose. Monitor for improvement in symptoms.
  6. If partial or no response, consider adding Dopamine agonist (Amantadine) or NMDA Antagonist (Memantine) or GABA-B Modulator (Zolpidem)
  7. Consider ECT in severe/malignant cases
  8. If response to Lorazepam, start scheduled Lorazepam 3mg – 20mg / day in divided doses
  9. Supportive measures include: Reversing hyperthermia, Hydration to prevent kidney injury, Optimize nutrition, Monitor oxygenation, Prevention strategies for deep vein thromboses and pressure ulcers, and closely monitor for (and make every attempt to prevent) muscle contractures and aspiration.

IMPORTANT NOTES:

  • Patients with chronic catatonia associated with schizophrenia are more resistant to Lorazepam and may need ECT
  • Consider NMDA Receptor antagonist (memantine) within 1-3 days of a failed lorazepam trial (and if ECT is NOT available) 
  • Amantadine, Memantine, Topiramate have limited evidence of efficacy (Case Studies/Case Series)

Electroconvulsive Therapy (ECT): ECT has a 90% response rate and is emergent first line treatment for: Malignant catatonia, Poor PO intake (refusing to eat or care for self), Partial response from medication trials

References

  1. Oldham, Mark A., and Hochang B. Lee. “Catatonia Vis-à-vis Delirium: The Significance of Recognizing Catatonia in Altered Mental Status.” General Hospital Psychiatry 37.6 (2015): 554-59. Web.
  2. Tandon, Rajiv, Stephan Heckers, Juan Bustillo, Deanna M. Barch, Wolfgang Gaebel, Raquel E. Gur, Dolores Malaspina, Michael J. Owen, Susan Schultz, Ming Tsuang, Jim Van Os, and William Carpenter. “Catatonia in DSM-5.” Schizophrenia Research 150.1 (2013): 26-30. Web.
  3. Fink, Max, and Michael Alan Taylor. “Catatonia: A History.” Catatonia (n.d.): 1-18. Web.
  4. Jaimes-AlbornozW, Serra-Mestres J. Prevalence and clinical correlations of catatonia in older adults referred to a liaison psychiatry service in a general hospital. Gen Hosp Psychiatry 2013;35:512–6.
  5. Grover S, Ghosh A, Ghormode D. Do patients of delirium have catatonic features? An exploratory study. Psychiatry Clin Neurosci 2014;68:644–51.
  6. Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review Sher, Yelizaveta et al. Psychosomatics , Volume 56 , Issue 6 , 615 – 625
  7. Catatonia in Medically Ill Patients An Evidence-Based Medicine (EBM) Monograph for Psychosomatic Medicine Practice. Academy of psychosomatic medicine
  8. Levenson, James L. Essentials of Psychosomatic Medicine. Washington, DC: American Psychiatric Pub., 2007. Print.
  9. Kirkhart, Rob et al. “The Detection and Measurement of Catatonia.” Psychiatry (Edgmont) 4.9 (2007): 52–56. Print.
  10. 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.
  11. 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.
  12. Focus Psychiatry Review, Dsm-5: Dsm-5 Revised Edition by Deborah J. Hales (Author, Editor), Mark Hyman Rapaport (Author, Editor)
  13. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  14. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences. Sixth Edition.
  15. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  16. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  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. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  20. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  21. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  22. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018
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Agitation or Aggression?

Let’s first define some important terms.

Agitation is defined as a state of pathologically intense emotional arousal and motor restlessness. Agitation differs from aggression in that there is no direction associated with agitation. That is, agitation is not directed at anyone in particular and is not characterized by purposeful actions toward someone else.

When a patient becomes hostile, threatening, and/or violent toward a person or object then we use the term aggression. Aggression is a state of mind implying intent to inflict harm. Violence is the action(s) taken to harm someone. That is, violence is defined as aggressive actions directed at someone or something. When violence is directed toward an intimate partner, we call it domestic violence. 

Impulsivity is a state characterized by a proneness to act without thought or self-restraint (i.e., acting or behaving without concern about the consequences of such actions). When someone lacks the ability to think things through we call them disinhibited.

Irritability is a state of abnormally low tolerance in which the individual is easily provoked to anger and hostility.

Now that we have a basic understanding of the terms, let’s discuss how to manage agitation and/or aggression in a clinical setting. 

Identifying the Underlying Cause 

The most important first step in the management of agitation or aggression is to identify the cause. Different causes may require different interventions. Agitation and aggression can be induced by drug intoxication or withdrawal states, medications, pain, acute psychotic or manic states, delirium states, antisocial/criminal behavior, or an inability to communicate needs. 

Common Causes of Agitation and Aggression

  • Drug Intoxication or Withdrawal
  • Medications
  • Pain
  • Psychosis
  • Mania
  • Delirium
  • Criminal Behavior and Malingering 
  • Inability to communicate needs

Managing Agitation and Aggression

When treating patients who are agitated or aggressive, we use a combination of behavioral and pharmacological interventions. When behavioral interventions fail to reduce agitation or aggression, then pharmacological interventions or physical restraints are used to protect the safety of the patient and staff. 

Behavioral Interventions

Give Space

When working with agitated patients, remember that they are in a heightened arousal state and easily triggered. Surrounding an agitated patient can induce panic and sense of being trapped. Always maintain your distance and give the patient space. The knee-jerk reaction for hospital staff is to rush into the room and team up to contain the situation but this often isn’t helpful.

Show Your Hands

Although this sounds trivial, it is actually important. You don’t know what an agitated patient is really thinking. Perhaps they are paranoid and think you are trying to hurt them. Placing your hands in your pocket or behind your back is not good practice. Always show your hands. This way the patient doesn’t mistake your hands in your pockets for your hands reaching for something hurtful. 

Defeated Wolf

While some would not agree with this, using the defeated wolf approach by slouching your shoulders and looking down can convey to the agitated person that you aren’t a threat. Puffing your chest out and staring the patient down signals dominance and aggression. 

Tone of Voice

Use an empathetic tone at a normal volume and show genuine concern. Letting the patient know how their behavior is affecting others is a useful tool. For example, “Mr. Thomas I can see you are very upset and this concerns me. We are all very worried and your behavior is making us very uncomfortable.”

Give Back Some Control

One of the most useful strategies in managing agitated patients is to offer choices. A major reason people become agitated or aggressive is because they sense a loss of control. By offering choices it can provide the patient some comfort in knowing that their autonomy is being respected. Some clinicians would recommend asking the patient what he or she needs but I have found that most patients simply yell to go away and let them go. By offering choices, the clinician maintains some control over the situation while also giving some control to the patient. For example, “Mr. T, can I offer you some food or water or maybe a quiet room? Would you like to go for a short walk together?” 

Decrease external stimuli

Loud voices, noisy surroundings, yelling, and crowded spaces are not helpful in de-escalating an agitated patient. The intensity of external stimuli can make or break a situation. Try to remain calm, speak in a normal tone and volume, and keep external noise to a minimum. Providing a quiet space can be soothing for agitated patients. 

Avoid being defensive or authoritative

Remember not to take anything personally. Patients can be agitated for many reasons, but it is unlikely that you are the reason. Being authoritative is not only unethical, it’s unhelpful. Make an effort to establish a collaborative relationship with the agitated individual. Let them know you are on their team and there to help. 

Pharmacological Interventions

While there is ongoing debate about the efficacy of antipsychotics in agitation, sometimes they are necessary to prevent harm to patients and staff. Pharmacological strategies should be used only when there is physical threat to the patient’s own wellbeing or the wellbeing of those around them. We use different medications or interventions depending on the cause. 

For Psychosis:

  • Haloperidol 2mg-10mg PO/IM ± Lorazepam 1-2mg
  • Olanzapine 2.5mg-10mg PO/IM/ODT (dissolvable)
  • Ziprasidone 10mg-20mg PO/IM
  • Chlorpromazine 25mg-100mg PO/IM
  • Risperidone 1mg-2mg M-Tab/PO

For Alcohol/CNS Depressant intoxication:

  • Haloperidol 2mg-10mg PO/IM

For Alcohol/Benzodiazepine withdrawal:

  • Lorazepam 1mg-2mg PO/IM/IV
  • Diazepam 5mg-10mg PO
  • Chlordiazepoxide 50mg PO

For Stimulant-intoxication or Withdrawal:

  • Lorazepam 1mg-2mg PO/IM/IV
  • Diazepam 5mg-10mg PO
  • Chlordiazepoxide 50mg PO

For Delirium:

  • Find and treat the medical cause
  • Behavioral Interventions
  • Atypical Antipsychotics (first-line pharmacological option)

For more on delirium, click here.

For Pain:

  • Optimize pain management
  • If from constipation, provide appropriate interventions to promote bowel motility
  • If related to the patients position in the bed, find a more comfortable position

For Medication-Induced Akathisia:

  • Stop the medication or reduce the dose. It is important to note that some medications can cause akathisia, which is a general restlessness where one feels the urge to keep moving and feels uncomfortable when trying to sit still. Akathisia can present similar to agitation and should be ruled out. Low dose propranolol or clonazepam can be helpful for medication induced akathisia. 

For the Repeatedly Aggressive/Threatening Individual:

  • Lithium 300mg-1,200mg/day
  • Chlorpromazine 25mg-100mg as needed
  • Propranolol 10mg-20mg three times daily
  • Selective Serotonin Reuptake Inhibitors (e.g., Sertraline, Citalopram)

There is no one right way to manage agitation. But the most important thing to keep in mind is that agitation usually stems from an individuals sense of losing control. Without sacrificing safety, help the agitated individual regain some of that control by acting as a collaborator rather than a dictator. For more information on agitation management, click the links below.

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. 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. Blumenfeld, Hal. Neuroanatomy Through Clinical Cases. 2nd ed. Sunderland, Mass.: Sinauer Associates, 2010.
  8. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  9. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  10. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  11. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  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.
  19. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
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What is Delirium?

Delirium is another word to describe an abrupt change in mentation. It can be thought of as analogous to other acute organ failures such as heart failure, liver failure, or kidney failure. In this case, delirium is an acute failure of brain function. The term Delirium, from latin Delirare (deviate from the furrow), describes a syndrome of acute alterations in attention, consciousness, and cognition. Delirium may be referred to as Altered Mental Status (AMS), Encephalopathy, or Altered level of consciousness (ALOC).

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 to days) in an individuals 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 or Cause of Delirium?

The pathophysiology or cause 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
  • 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. Thorough review of medications may provide insight into the cause of confusion. For example, benzodiazepines, opioids, and antihistamines are medications that can induce a confusion state in older adults and should be used judiciously. 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

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. 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. Blumenfeld, Hal. Neuroanatomy Through Clinical Cases. 2nd ed. Sunderland, Mass.: Sinauer Associates, 2010.
  8. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  9. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  10. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  11. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  12. 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.
  13. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  14. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  15. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  16. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  17. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  18. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  19. Stein, Lerer, and Stahl. Essential Evidence-Based Psychopharmacology. Second Edition. 2012.
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Which Medications Require Blood Level Monitoring?

Most medications used to treat mental disorders do not require blood level monitoring. This is mainly due to the inconsistency and heterogeneity of responses to different doses of psychiatric medications.

Only a few medications have sufficient evidence suggesting a therapeutic range and threshold for toxicity. In fact, blood level monitoring is used more for preventing toxicity than ensuring therapeutic efficacy. 

Lithium has a narrow therapeutic index, which means the threshhold for therapeutic effect and toxicity are close together. The normal therapeutic blood level for lithium is between 0.6-1.2.

Valproic acid (Depakote) does not have an agreed upon therapeutic level, but most experts report toxic effects with blood levels over 150.

Clozapine does not require monitoring of drug levels per se, but instead requires repeated neutrophil counts because neutropenia (i.e., low white blood cells) and agranulocytosis are rare yet serious adverse effects of clozapine treatment. 

Below is a table outlining the most common medications requiring blood level monitoring, their recommended therapeutic ranges, and the recommended frequency of monitoring. 

[table id=21 /]

*(—) No definitive evidence correlating levels with efficacy 

Lithium Level Monitoring

[table id=46 /]

Clozapine & Absolute Neutrophil Count (ANC) Monitoring

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. Focus Psychiatry Review, Dsm-5: Dsm-5 Revised Edition by Deborah J. Hales (Author, Editor), Mark Hyman Rapaport (Author, Editor)
  5. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  6. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  7. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  8. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  9. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  10. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  11. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  12. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  13. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  14. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  15. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  16. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  17. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  18. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
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Common Drug-Drug Interactions in Psychiatry

Polypharmacy refers to the use of multiple medications in one individual. Medications, whether for blood pressure or depression, do not work in a vacuum. When we swallow, inhale, or inject medications they make their way through our bodies in complex ways. Most medications are transported in blood attached to proteins, but many others are transported unattached in their free form. As medications make their way to their target organs, they come in contact with all kinds of tissues, cells, and fluids before they are metabolized and/or eliminated from the body.

Prescribing multiple medications for one individual increases the risk for adverse drug interactions. Some medications might displace a medicine from transport proteins while others might alter the activity of enzymes, such as CYP450 enzymes, that metabolize other drugs. Alternatively, some medications might compete with other drugs at their receptor sites and alter their effects.

While the variety of mechanisms are beyond the scope of this post, we review some of the most common drug interactions for medications used to treat mental health disorders. 

Valproic acid (VPA) + Lamotrigine:

  • Valproic acid (VPA) increases lamotrigine levels

  • Increases risk of Steven-Johnson’s Syndrome (SJS/TEN)

  • When using both, decrease the dose of lamotrigine by 50%

Carbamazepine (CBZ) is an inducer of CYP3A4:

  • CBZ induces its own metabolism

  • CBZ induces the metabolism of numerous other medications including oral contraceptives, clozapine, alprazolam, buspirone, and clonazepam

Lithium + NSAIDs (not aspirin), ACE Inhibitors, Thiazide diuretics, low sodium diet:

  • Increases lithium levels

Lithium + caffeine, theophylline, high sodium diet:

  • Decreases lithium levels

Grapefruit Juice

  • Grapefruit juice is a potent inhibitor of CYP3A4 and P-glycoprotein

  • Grapefruit juice increases blood levels of many medications metabolized by CYP3A4

Smoking Tobacco cigarettes:

  • Induces activity of CYP1A2

  • The induction does not appear to be from the nicotine, but from the hydrocarbons in smoke

  • Decreases blood levels of medications metabolized by CYP1A2 (Olanzapine, Clozapine, Caffeine)

Tyramine:

  • Increased risk of hypertensive crisis when eating tyramine containing foods while taking MAOIs, SSRIs, TCAs, Pseudoephedrine, and Stimulants

  • Tyramine-rich foods include banana peel, beer, fava beans, aged cheese, sauerkraut, sausage, soy sauce, concentrated yeast extract.

Fluoxetine, Paroxetine, and Bupropion are potent inhibitors of CYP2D6:

  • They can raise blood levels of medications metabolized by CYP2D6.

  • Tamoxifen and Codeine are prodrugs requiring metabolism by CYP2D6. Efficacy of these drugs may be decreased when used with inhibitors of CYP2D6.

Antimicrobial-Psychotropic Drug Interactions:

  • Antimalarials: Increase phenothiazine (e.g. chlorpromazine) levels

  • Azoles: Increase alprazolam, midazolam, and buspirone levels

  • Clarithromycin, Erythromycin: Increase alprazolam, midazolam, carbamazepine, clozapine, and buspirone levels

  • Quinolones: Increase clozapine and benzodiazepine levels but decreases benzodiazepine effects

  • Isoniazid: Increases haloperidol and carbamazepine levels. Isoniazid + disulfiram can cause ataxia

  • Linezolid: Serotonin syndrome if used with serotonergic drugs

Other Interactions/Adverse Reactions:

  • Erythromycin, Clarithromycin, and Ketoconazole: QT prolongation and ventricular arrythmias with TCAs and antipsychotics

  • Linezolid is an irreversible MAO-A inhibitor: Serotonin syndrome and Hypertensive crisis

  • Isoniazid is a weaker MAO inhibitor: Reports of Serotonin syndrome and hypertensive crisis

Common Side Effects of Antiretroviral Drugs

[table id=30 /]

Drug Interaction Tables

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. Focus Psychiatry Review, Dsm-5: Dsm-5 Revised Edition by Deborah J. Hales (Author, Editor), Mark Hyman Rapaport (Author, Editor)
  5. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  6. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  7. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  8. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  9. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  10. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  11. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  12. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  13. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th
  14. Goldberg & Ernst. Managing Side Effects of Psychotropic Medications. 1st 2012. APP.
  15. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia :Lippincott Williams & Wilkins, 2000.
  16. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  17. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  18. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
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Anorexia Nervosa vs Bulimia Nervosa

  • Anorexia Nervosa
  • Bulimia Nervosa

Anorexia Nervosa is a disorder of restricted energy intake relative to requirements which leads to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. There is often an intense fear of gaining weight or of becoming fat with persistent behavior that attempts to interfere with weight gain despite already being at a significantly low weight. There is often a disturbance in the way in which one’s body weight or shape is experienced with undue influence of body weight or shape on self-evaluation, and a persistent lack of recognition of the seriousness of the individual's low body weight.

Types of Anorexia Nervosa

Restricting type: The individual has not engaged in recurrent episodes of binge eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas). This subtype describes presentations in which weight loss is accomplished primarily through dieting, fasting, and/or excessive exercise.

Binge-eating/purging type: The individual has engaged in recurrent episodes of binge eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas).

 

DSM-5 Criteria:

A. Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. Significantly low weight is defined as a weight that is less than minimally normal or, for children and adolescents, less than that minimally expected.

B. Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight.

C. Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight.

Types of Anorexia Nervosa

Restricting type: During the last 3 months, the individual has not engaged in recurrent episodes of binge eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas). This subtype describes presentations in which weight loss is accomplished primarily through dieting, fasting, and/or excessive exercise.

Binge-eating/purging type: During the last 3 months, the individual has engaged in recurrent episodes of binge eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas).

 

Severity of Anorexia Nervosa

The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or, for children and adolescents, on BMI percentile. The ranges below are derived from World Health Organization categories for thinness in adults; for children and adolescents, corresponding BMI percentiles should be used. The level of severity may be increased to reflect clinical symptoms, the degree of functional disability, and the need for supervision.

Mild: BMI>17kg/m2

Moderate: BM116-16.99 kg/m2

Severe: BM115-15.99 kg/m2

Extreme: BMI < 15 kg/m2

Bulimia Nervosa is an eating disorder characterized by recurrent episodes of binge eating, which is defined by both eating an amount of food that is definitely larger than what most individuals would eat in a similar period of time under similar circumstances AND a sense of lack of control over eating during that period of time (i.e., a feeling that one cannot stop eating or control what or how much one is eating). In addition, there are recurrent inappropriate compensatory behaviors in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise. Self-evaluation is unduly influenced by body shape and weight in most cases. 

DSM-5 Criteria:

A. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:

  1. Eating, in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than what most individuals would eat in a similar period of time under similar circumstances.
  2. A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating).

B. Recurrent inappropriate compensatory behaviors in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise.

C. The binge eating and inappropriate compensatory behaviors both occur, on average, at least once a week for 3 months.

D. Self-evaluation is unduly influenced by body shape and weight.

E. The disturbance does not occur exclusively during episodes of anorexia nervosa.

Severity of Bulimia Nervosa:

The minimum level of severity is based on the frequency of inappropriate compensatory behaviors (see below). The level of severity may be increased to reflect other symptoms and the degree of functional disability.

Mild: An average of 1-3 episodes of inappropriate compensatory behaviors per week.

Moderate: An average of 4-7 episodes of inappropriate compensatory behaviors per week.

Severe: An average of 8-13 episodes of inappropriate compensatory behaviors per week.

Extreme: An average of 14 or more episodes of inappropriate compensatory behaviors per week.

*For these disorders, be sure to rule out medical causes and then use Behavioral Therapy as primary treatment.

**For these disorders, treatment is reviewed below

Treatment of Eating Disorders

American Academy of Pediatrics

Criteria for Inpatient Medical Hospitalization:

Anorexia Nervosa Bulimia Nervosa
  1. Heart rate < 50 beats/min daytime; < 45 beats/min nighttime
  2. Systolic blood pressure < 90 mm Hg
  3. Orthostatic changes in pulse (> 20 beats/min) or blood pressure (> 10 mm Hg)
  4. Arrhythmia
  5. Temperature < 96°F
  6. < 75% ideal body weight or ongoing weight loss despite intensive management
  7. Body fat < 10%
  8. Refusal to eat
  1. Syncope
  2. Serum potassium < 3.2 mmol/L
  3. Serum chloride < 88 mmol/L
  4. Esophageal tears
  5. Cardiac arrhythmia including prolonged QTc
  6. Hypothermia
  7. Suicide risk
  8. Intractable vomiting
  9. Hematemesis
  10. Failure to respond to outpatient treatment

References

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  2. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  3. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  4. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  5. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  6. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th Edition.
  7. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia.
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What are Personality Disorders?

What is personality?

Personality has been defined and revised numerous times over the years. The general consensus is that personality is one’s stable and predictable emotional, cognitive, and behavioral traits that remain consistent over time.

One’s personality develops from a complex and dynamic interplay between nature (i.e. genetics) and nurture (i.e. environment). Typically, personality traits remain relatively stable throughout adulthood.

Personality Disorders represent deeply ingrained, pervasive, and rigid patterns of relating to oneself and others that are maladaptive and cause significant impairment in functioning.

It is important to remember that personality traits are not considered pathological or “disordered” unless they cause significant distress or dysfunction in a person’s life. Individuals with pathological or disordered personality traits often lack insight into their problems and the way their behavior affects others (including themselves). That is, their symptoms are considered ego-syntonic. 

There has been ongoing debate and controversy surrounding the idea of discrete disorders of personality given that many people meet criteria for more than one personality disorder. In fact, there is a high likelihood that personality disorders will be removed from the Diagnostic Manual in upcoming revisions.

Nonetheless, we organize personality disorders into three “Clusters” (i.e., Cluster A, Cluster B, and Cluster C) with each cluster sharing similar core features. 

  • Cluster A: Schizoid, Schizotypal, and Paranoid.

  • Cluster B: Antisocial, Borderline, Histrionic, and Narcissistic.

  • Cluster C: Avoidant, Dependent, and Obsessive-Compulsive.

General Personality Disorder in DSM-5

Below are the DSM-5 Criteria for “General Personality Disorder:”

A. An enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culutre. This pattern is manifested in two (or more) of the following areas:

  1. Cognition (i.e., ways of perceiving and interpreting self, other people, and events)
  2. Affectivity (i.e., the range, intensity, lability, and appropriateness of emotional response)
  3. Interpersonal Functioning
  4. Impulse control

B. The enduring pattern is inflexible and pervasive across a broad range of personal and social situations

C. The enduring pattern leads to clinically significant distress or impairment in social, occupational, or other important areas of functioning.

D. The pattern is stable and of long duration, and its onset can be traced back at least to adolescence or early adulthood.

E. The enduring pattern is not better explained as a manifestation or consequence of another mental disorder

F. The enduring pattern is not attributable to the physiological effects of a substance (e.g., drug of abuse or medication) or another medical condition (e.g., head trauma). 

Specific criteria for each personality disorder are tabulated below:

Cluster A Personality Disorders

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Cluster B Personality Disorders

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Cluster C Personality Disorders

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Additional Information

In general, each personality disorder has a prevalence of approximately 1%. Personality disorders are very difficult to treat as they require changing ingrained patterns of behavior. Therefore, psychotherapy and group therapy remain the primary treatments for managing personality disorders. 

Here is some additional information worth mentioning:

Schizotypal Personality Disorder and Schizoid Personality Disorder

These personality disorders commonly occur in families with history of Psychotic disorders. This tells us that there are likely genetic links between primary psychotic disorders and cluster A personality disorders. Some experts would argue that Schizotypal and Schizoid personality disorders are part of a spectrum including schizophrenia and related psychotic disorders. 

Histrionic Personality Disorder

The most common defense mechanism used by individuals with histrionic personality disorder is “regression.”

Borderline Personality Disorder

Most common defense mechanisms used by individuals with borderline personality disorder are “splitting” and “projection.” Projective identification is a common interpersonal dynamic as well. Other common behaviors include self harm behaviors, manipulation, gaslighting, and substance abuse. A history of sexual trauma or abuse is not uncommon in individuals with borderline personality traits. 

Antisocial Personality Disorder

Antisocial personality disorder usually begins as Conduct Disorder in childhood. Often times there is history of animal cruelty, fighting, and sexual abuse in childhood. Substance abuse and criminal activity is very common. Deceptive tactics and manipulation are often used to get what they want. 

Schizoid vs Avoidant Personality Disorder

Individuals with schizoid personality traits want to be alone and are content with being alone. Individuals with avoidant personality traits want to be alone but this is due to anxiety and fear (they would rather be social!)

Obsessive Compulsive Disorder (OCD) vs Obsessive Compulsive Personality Disorder (OCPD)

In Obsessive Compulsive Disorder, individuals recognize their thoughts and behaviors as irrational and disturbing. That is, their symptoms are ego-dystonic. In Obsessive Compulsive Personality Disorder (OCPD) individuals see their traits as essential to their success. That is, their symptoms are ego-syntonic

Treatment of Personality Disorders

Psychotherapy remains the first line and most effective treatment for personality disorders.

Pharmacological treatment is not first line treatment for personality disorders but because many personality disorders are comorbid with other psychiatric disorders, pharmacological treatment should be used to address any comorbid mood or anxiety disorders. 

Below are the therapy modalities and pharmacological treatments of choice for each personality cluster:

Cluster A disorders

  • Cognitive Behavioral Therapy
  • Group Therapy
  • Antipsychotics may be used for transient psychotic symptoms

Cluster B disorders

  • Dialectical Behavioral Therapy
  • Contingency-Based Therapies
  • Cognitive Behavioral Therapy
  • Group Therapy
  • Of all the personality disorders, borderline personality disorder is the most likely to respond to mood stabilizers (e.g., lamotrigine, lithium, valproate), Selective Serotonin Reuptake Inhibitors (e.g. Fluoxetine), and atypical antipsychotics (e.g., olanzapine) 

Cluster C disorders

  • Cognitive Behavioral Therapy
  • Assertiveness Training
  • Group therapy
  • Exposure Therapy
  • Selective Serotonin Reuptake Inhibitors (SSRIs) and beta-blockers are often used for comorbid anxiety and depressive disorders.

References

  1. Focus Psychiatry Review, Dsm-5: Dsm-5 Revised Edition by Deborah J. Hales (Author, Editor), Mark Hyman Rapaport (Author, Editor)
  2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  3. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
  4. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  5. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  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. Stein, Lerer, and Stahl. Essential Evidence-Based Psychopharmacology. Second Edition. 2012.
  9. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
  10. Psychology Today Website