Dialectical Behavioral Therapy (DBT)

Dialectical Behavioral Therapy

Dialectical Behavioral Therapy (DBT) is a cognitive-behavioral treatment developed by Marsha Linehan, Ph.D., in the 1980s to help people who often experience extremely intense negative emotions that are nearly impossible to manage. These intense and uncontrollable negative emotions are often experienced when the individual is interacting with others—friends, romantic partners, family members. Not surprisingly, who experience intense emotions often struggle in maintaining healthy relationships.

The “D” means “dialectical.” A dialectic is a synthesis or integration of opposites. A DBT-oriented therapist consistently works with an individual to find ways to hold two seemingly opposite perspectives at once, promoting balance and avoiding black and white (all-or-nothing) styles of thinking. In service of this balance, DBT promotes a “both-and” rather than an “either-or” outlook. The dialectic at the heart of DBT is acceptance and change.

Dialectical strategies help us get unstuck from extreme positions. They help us stay “in-balance” so we can reach our ultimate goals as quickly as possible. The Wise Mind is a classic example.

Dialectical behavior therapy (DBT) provides us with new skills to manage painful emotions and decrease conflict in our relationships. DBT specifically focuses on providing skills in four key areas.

  1. Mindfulness: Mindfulness focuses on improving our ability to accept and be present in the current moment.
  2. Distress Tolerance: Distress tolerance is geared toward increasing our tolerance of negative emotion, rather than trying to escape from it.
  3. Emotion regulation: Emotion regulation covers strategies to manage and change intense emotions that are causing problems in our lives.
  4. Interpersonal effectiveness: Interpersonal effectiveness consists of techniques that allow us to communicate with others in a way that is assertive, maintains self-respect, and strengthens relationships.

Using a DBT approach, a therapist uses acceptance and behavioral change strategies by validating and accepting the individual as he or she is.  A DBT therapist appreciates that too much focus on change results in the individual feeling misunderstood and invalidated. Working with people with extreme emotional sensitivity requires careful attention to the balance between acceptance and change. It also requires an assessment of personal boundaries

DBT was originally developed to treat borderline personality disorder. However, research shows that DBT has also been used successfully to help people suffering from depression, bulimia, binge-eating, bipolar disorder, post-traumatic-stress disorder, abandonment/attachment problems, and substance abuse. 

Try the Wise Mind Exercise!

How to maintain a healthy work-life balance to prevent burnout

How to maintain a healthy work-life balance to prevent burnout

 
With the COVID-19 pandemic blurring the line separating work life and personal life, work burnout is becoming the new epidemic. We will review common signs and symptoms of work burnout and offer some strategies for managing this new epidemic. 

What is Work Burnout?

Work burnout is considered a type of work-related stress characterized by a sense of reduced accomplishment and loss of personal identity. Burnout is not a medical diagnosis by itself, but it may exacerbate, or be a nidus of, numerous health-related problems.

Interestingly, researchers propose that individual factors, such as personality traits and family life, influence who experiences work burnout. Let’s consider how to know if you are suffering from work burnout and what you can do to relieve the suffering. 

What are common signs and symptoms of work burnout?

  • Becoming cynical or critical at work
  • Dragging yourself to work and having trouble getting started
  • Irritability or impatience with co-workers, customers or clients
  • Fatigue
  • Difficulty concentrating 
  • Lacking satisfaction from your achievements
  • Using food, drugs or alcohol to feel better or to void negative feelings
  • Sleep problems
  • Unexplained headaches, stomach or bowel problems, or other physical complaints
If any of the above symptoms resonate with you then consider whether you’re suffering from work burnout. It is always recommended to talk with your healthcare provider because these symptoms can also be related to health problems such as depression.

Who is at risk of developing work burnout?

  • Those who have a heavy workload and work long hours
  • Those who struggle with work-life balance
  • Those who work in a helping profession, such as health care
  • Those who feel they have little or no control over their work

What are some consequences of work burnout?

Work burnout can have significant consequences, including:
  • Excessive stress
  • Fatigue
  • Insomnia
  • Sadness, anger or irritability
  • Alcohol or substance use disorders
  • Heart disease
  • High blood pressure
  • Type II diabetes
  • Vulnerability to medical problems, including infections

What are some strategies for managing work burnout?

  • Recognize the signs and symptoms of burnout and assess whether they are negatively impacting your life. This is an obvious but often neglected first step!
  • Discuss specific concerns with a supervisor (if possible). Perhaps you can reassess expectations and develop solutions together. 
  • Prioritize daily tasks (more on this later)
  • Seek support. Whether you reach out to co-workers, friends or loved ones, support and collaboration might help you cope. If you have access to an employee assistance program, take advantage of relevant services.
  • Engage in one or more stress-reducing activities for at least 20 minutes each day. This may include yoga, meditation, tai chi, martial arts, mindfulness exercises, boxing, weight training, cross-fit, running, swimming, other aerobic exercise, sports, creative writing, painting, drawing, listening to music, playing an instrument, or reading for pleasure. 
  • Get quality sleep. We spend about a third of our lives sleeping. Sleep allows our body to reset. Interestingly, sleep is important for our memory, our immune system, and our ability to regulate our emotions.
  • Healthy diet. Junk food is comforting, but it doesn’t help your cause. Having the occasional “cheat meal” is important, but limit those sweets and saturated fats as much as possible. A high protein, high fiber, moderate fat, and low carbohydrate diet can improve your energy levels, concentration, memory, and mood!
  • Set healthy work-life boundaries. Setting healthy work-life boundaries will not only improve your mental health but prevent burnout and promote more effective and efficient work!
Let’s discuss healthy work-life boundaries in a bit more detail…

Work-life boundaries

Boundaries are the rules we set for ourselves in our relationships, our work, and our personal lives. Healthy boundaries mean preventing others from projecting beliefs, judgements, or expectations onto you. Many people will use “I don’t have time” as the reason for not taking care of their own needs. If you can’t make time for yourself, then what you are really saying is “my needs don’t matter.” This eventually leads to resentment and anger. A person with healthy boundaries can say “no” to others when needed without allowing the fear of disappointment to overpower your personal needs. Remember, if someone feels disappointed or let down because you chose to take care of yourself, then it probably means firmer boundaries were needed anyway. 

Take an honest look at your self-care habits

The first step in setting healthier boundaries is to honestly assess your self-care practices. Use this tool to assess your self-care habits.

Prioritizing your values

Boundaries should be based on your beliefs and values–the things that are important to you. These may or may not align with others and that is okay. They are YOUR boundaries.  The first step is to make a priority list. Example below:

  • Spending time with family
  • Personal Free time/Hobbies
  • Exercise
  • Productive and Efficient work

Prioritizing your time

Each day, it is important to make time for your top priorities. To do this, you will need to create a “skeleton” schedule. This does not mean scheduling your day minute by minute or hour by hour. You don’t want to become a prisoner of your own schedule! Here is an example based on the priorities listed above:

Morning 

  • Wake up at 6:30AM
  • Exercise for 30 minutes before work
  • Check and respond to emails for 30 minutes 
  • Work from 8AM-11AM with 15-minute breaks every 45 minutes 

Noon

  • Spend 30 to 45 minutes eating lunch and visiting with a friend or family member
  • Check and respond to emails for 30 minutes prior to starting afternoon work

Afternoon

  • Work from 1PM-4PM with 15-minute breaks every 45 minutes
  • End all work at 5PM and spend 30 minutes checking and responding to emails one last time for the day

Evening

  • Spend at least one (1) hour with a friend or family member
  • Spend 30 minutes playing guitar (or other hobby)
  • Get ready for bed at 10:00pm
  • Leisure reading for 30 minutes in bed
  • Lights out by 10:30PM

Stop Obsessively Checking Your Email

Schedule the times you plan to check your email. One of the biggest mistakes people make is obsessively checking email. This is anxiety-provoking and inefficient. It disrupts your focus and is simply unnecessary. Use the auto-respond function to inform those who email you of when you check your email. You can also instruct people to call you directly if it is urgent.

Let Smartphones Be Smartphones

As with email, limit time on your phone as much as possible. When you need to focus on completing a task, silence your phone and place it facedown next to you. If answering phone calls is important for your work, place your phone on vibrate and keep it in your pocket. When not working, set a time to put your phone on silent in a drawer or out of view for at least 30 minutes. By doing this, you’ll learn that you DO NOT need to have your phone on you at all times.

Your Computer Needs a Break Too

Your computer should only be used for work during work hours only. When the workday is over, shut down your computer and/or put it away. If you need to use the computer for personal use, then use it for personal use ONLY. Some people find it helpful to have two devices – one for work and one for play. But this may not be possible.

Remaining Consistent

Try your best to remain consistent with your schedule! There will always be some flexibility but do your best to remain consistent. Try not to get down on yourself if you struggle at first to be consistent. Simply recognize when you’re deviating from the path and make adjustments to get back on track.

Using technology to help you

Many smartphones have reminder functions. Try setting reminders for when to take breaks, check emails, spend time with family, or exercise. There are many apps out there that can help with prioritizing your daily tasks as well!

Sharing your boundaries with others

It is important to share your new strategies with your family, friends, co-workers, and supervisor(s). Ask your friends and family to keep an eye on your behaviors so they can point out when you might need to make some adjustments. Inform your co-workers and supervisor(s) so they can provide input and suggestions. While it is important to maintain healthy boundaries, it is also important to know how to compromise. BUT…compromising does not mean trashing all your boundaries.

Whenever you have the urge to work during non-work hours, make a habit of asking yourself the following:

  • Is this in line with my values and priorities?
  • How important, on a scale from 1-10, is it that I complete this RIGHT NOW? (Anything 6 or below can wait).

Beginning and ending each day with anything BUT work

It is essential to begin and end your day with something positive. Something you enjoy. If the first thing you do each morning is check your email and the last thing you do is check your email, then you are setting yourself up for burnout. Do not let the first and last activity of each day be something work-related. 

Exercise for Couples

The Couple’s Exercise

Relationships require work. They require patience, humility, sacrifice, empathy, and compromise. But here’s the thing…healthy relationships are only possible when we have a healthy relationship with ourselves. Afterall, how can we expect to maintain healthy relationships with others if we don’t maintain a healthy relationship with ourselves?

So, before we start blaming the problems in our relationships on others, we need to stop and ask ourselves this question:

Do I genuinely love myself?

If not (or you aren’t sure) then you’ll have to accept that your relationships will continue to suffer until you work on the relationship you have with yourself. 

Relationships are like tending to a garden. We have to make time for them, sacrifice for them, and nurture them if we want them to thrive. 

This exercise was designed to help couples connect with each other–to remind each other of the reasons they fell in love in the first place. But remember, it takes two to tango. So, allow yourself to be vulnerable, to be open to suggestions, and to be an empathic listener. If you can’t do those things, then prioritize working on yourselves first. Afterall, you can’t expect to cultivate a healthy relationship with someone else if your authentic self doesn’t come to the table. 

The Exercise

A Mindful Walk

A Mindful Walk

Mindfulness means paying attention to the present moment without judgement. It means taking a step back and noticing things. The goal of mindfulness is to simply observe. This helps reduce the rumination and worry that often accompanies depressed and anxious moods. 

What are Bipolar Disorders? What is the Bipolar Spectrum?

What are Bipolar Disorders? What is the Bipolar Spectrum?

Before we discuss bipolar disorders, let’s review the terms “Mood” and “Affect”

Affects and moods refer to different aspects of emotion. Affect is communicated through facial expression, vocal inflection, gestures, and posture. Affect is intended to allow humans and nonhuman primates to appraise satisfaction, distress, disgust, and dangerousness in others. Thus, joy, sadness, anger, and fear are basic affects that serve a communicative function. Affects tend to be short-lived expressions reflecting momentary emotional contingencies.

Moods convey sustained emotions; their more enduring nature means they are experienced long enough to be felt inwardly. Moods are also manifested in subtle ways, and their accurate assessment often requires empathic understanding by observers. The words that people use to describe their inner emotions may coincide with the technical terms used by researchers or clinicians and often vary from one culture to another. 

Sometimes, the inward emotion and the prevailing affective tone may be discordant or incongruent. This conflict could be due to deliberate simulation (i.e., the person does not wish to reveal his or her inner emotion), or it could result from a pathological lesion or process that has altered emotions and their neural substrates.

AFFECT: A person’s immediate expression of emotion

MOOD: The more sustained emotional makeup of a person’s personality 

 

What are Mood Disorders?

Mood disorders are group of psychiatric disorders in which disturbances of mood or affect are severe and persistent enough to cause significant problems in an individual’s life. Moods themselves are not pathological and many of us have experienced a range of mood states. But when moods become severe and persistent enough to cause dysfunction and issues in an individual’s life, then we use the term “mood disorder.”
 
Symptoms of mood disorders usually occur in discrete periods we call episodes. Episodes can last for weeks, months, or even years. During these “episodes,” there is a significant change in the individual’s mood which may negatively impact work performance, relationships, or other important areas of functioning. The most common mood disorder is Major Depressive Disorder (MDD), often referred to as “Unipolar depression.”
 
Bipolar disorders are also mood disorders that differ from unipolar depression by the presence of elevated mood states called hypomania or mania.

Bipolar Disorder

Bipolar disorder is a mental illness characterized by dramatic shifts in a person’s mood, energy and ability to think clearly. People with bipolar disorder experience high and low moods—known as mania and depression, respectively—which differ from the typical ups-and-downs most people experience. The average age-of-onset is about 25. The cause of bipolar disorder is not fully understood but there are a number of contributing factors that include genetic influences, environmental factors linked to stress, and biochemical factors that include changes in brain chemicals (including hormones). If left untreated, bipolar disorder usually worsens. However, with a good treatment plan including psychotherapy, medications, a healthy lifestyle, sobriety, a regular schedule and early identification of symptoms, many people live well with the condition.

What is Mania and Hypomania?

Mania is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood with abnormally and persistently increased goal-directed activity or energy that lasts at least 1 week. Hypomania is similar to mania but less severe. A hypomanic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy that lasts at least four consecutive days. Hypomanic episodes are typically not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic. During a manic or hypomanic episode, a combination of the following symptoms is present and represents a noticeable change in behavior (see below).

 

If drugs or medications cause the above symptoms, then we consider this a medication (or substance)-induced manic or hypomanic state. However, a full manic or hypomanic episode that emerges due to medication (e.g., antidepressants) or drugs (e.g., cocaine, amphetamines) but persists beyond the physiological effect of the medication or drug is sufficient for a bipolar diagnosis.

Bipolar Subtypes

Our understanding of mood disorders continues to evolve over time. Most experts consider bipolar disorder to be on a spectrum. As of the writing of this post, the Diagnostic and Statistical Manual Fifth Edition (DSM-5) classifies bipolar disorders into Bipolar I Disorder, Bipolar II Disorder, Cyclothymia, and bipolar disorder due to a medical condition.

Rapid cycling in bipolar disorder (BD) is a descriptor that defines a subset of patients that have a large number of episodes over short periods of time. Specifically, rapid cycling is defined as having 4 or more episodes in a 12 month period, but many patients may have significantly more episodes. Individuals with rapid cycling generally have a younger age of onset, greater disease burden, and greater exposure to antidepressants. Cannabis, alcohol, caffeine, steroids, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and Tricyclic Antidepressants have been associated with inducing rapid cycling. 

The Neurobiology of Bipolar Disorder

Bipolar disorder is a complex disorder. A combination of genetic risk factors and environmental risk factors (e.g., childhood trauma) likely result in changes at numerous levels (intracellular, intercellular, network, etc.) that manifest behaviorally as bipolar disorder. The underlying biochemical abnormalities that cause or contribute to bipolar disorder remain unclear. However, studies have suggested neurobiological differences between unipolar and bipolar depression. This is further supported by the lack of efficacy of classic antidepressants in bipolar depression. In fact, there is evidence that classic antidepressants may induce mania and/or cause rapid cycling in patients with underlying bipolar disorder.

Human studies have found increased concentrations of noradrenaline (norepinephrine) and dopamine (DA) and decreased concentrations of serotonin (5-HT) in manic patients. This suggests that norepinephrine and dopamine dysregulation may play a primary role in manic symptoms. In addition to monoamine dysregulation, there is evidence implicating the glutamate and GABA systems in the pathophysiology of bipolar disorder. Animal studies suggest increased glutamatergic neurotransmission via NMDA receptors in manic patients. In addition, the efficacy of anticonvulsants, NMDA antagonists (e.g., ketamine), and benzodiazepines in the treatment of bipolar disorder suggests that glutamate and GABA systems are involved.

Circadian rhythms are consistently disturbed in patients with bipolar disorder. Researchers are investigating whether circadian rhythm disturbances might lead to mania given the fact that lithium deactivates the transcription factor GSK3B enzyme which is thought to reset the circadian clocks and restore normal brain functioning.

Functional Neuroimaging Studies have demonstrated or suggested that the following areas are implicated in bipolar disorder: prefrontal cortex, limbic areas such as the hippocampus, amygdala, anterior cingulate, and the ventral striatum (nucleus accumbens). A number of brain circuits have been implicated in the pathophysiology of bipolar disorder. Many of these circuits are involved in the regulation of emotion and cognition. Decreased activation of the orbitofrontal (OFC) circuits during a go-no go test in manic patients may explain the impulsive behaviors. Recall that the OFC is an important region within the prefrontal cortex involved in impulse-control and compulsive behaviors. The dorsolateral prefrontal cortex is involved in attentional processes and its dysfunction may also play a role in the pathophysiology of bipolar disorder. Decreased size and activity of the prefrontal cortex (PFC) has been demonstrated in patients with bipolar disorder—similar to that found in patients with unipolar depression. Interestingly, after four weeks of lithium treatment (but no valproic acid) there was an increase in gray matter volume in bipolar patients. Amygdalae are larger and more active in the bipolar patients. Bipolar disorder may be the result of abnormal interactions between the PFC and subcortical regions such as the amygdala—an abnormality not usually seen with unipolar depression. Reasons for the reduction in brain volumes and cell loss remain a mystery but could be from environmental stressors, neurodevelopmental abnormalities, and/or dysfunction in neurotransmitter systems.

Treatment of Bipolar Disorder

The management of bipolar disorder is multidimensional. The main objectives of pharmacotherapy (medication management) in bipolar disorder are to treat the acute manic/hypomanic and depressive episodes and minimize their recurrence.

Manic episodes are treated with one or more of the following: Lithium, valproate (Depakote), carbamazepine (Tegretol), lamotrigine (Lamictal), asenapine (Saphris), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), ziprasidone (Geodon), cariprazine (Vraylar), or aripiprazole (Abilify), clonazepam (Klonopin), diazepam (Valium), or lorazepam (Ativan).

Bipolar depressive episodes are treated with one or more of the following: Lithium, cariprazine (Vraylar), quetiapine (Seroquel), lurasidone (Latuda), Fluoxetine-Olanzapine combination (OFC), or lamotrigine (Lamictal).

Comorbid symptoms such as inattention, low energy, and low motivation can be safely treated with classic psychostimulants as long as a mood stabilizer is also prescribed. Severe anxiety, including social anxiety, can be safely managed with the addition of clonidine, propranolol, gabapentin, pregabalin, or benzodiazepines. In general, antidepressants should be avoided.

Neuromodulatory modalities such as neurofeedback, Transcranial Magnetic Stimulation (TMS), and ketamine infusion therapy should be considered if medication and therapy are not effective (or only partially effective).

While medication, neuromodulatory modalities, and drug abstinence are important in the management of bipolar disorder, they are considered components of a comprehensive treatment plan. As such, individual and/or family psychotherapy and psychoeducation should be considered.

Bipolar Depression

Bipolar Mania and Mixed States

Bipolar Maintenance

Observational studies suggest that with each episode of illness the time between episodes shortens. This highlights the importance of relapse prevention, which may improve long-term prognosis. For Mania Prevention: Lithium (Reduces suicide rates and overall mortality), Aripiprazole, Quetiapine, Olanzapine, Valproic Acid.  For Depression Prevention: Quetiapine, Lamotrigine, Lithium (Reduces suicide rates and overall mortality), Lurasidone

Final Comments

It is important to remember that the management of neuropsychiatric disorders is multifactorial, and medication is only one component. As stated previously, integrating treatment modalities such as psychotherapy, mentorship, sobriety, mindfulness-based stress reduction, and the pursuit of passionate hobbies/interests are all very important in the management of bipolar disorder.

BIPOLAR DISORDER DIAGNOSIS AND TREATMENT GUIDELINES (PDF)

References

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  2. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences. Sixth Edition.
  3. Bear, Mark F.,, Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Fourth edition. Philadelphia: Wolters Kluwer, 2016.
  4. Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. Journal of Clinical Psychiatry. 1998;59(Suppl):11–14.
  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. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  7. Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: from monoamines to glutamate. Experimental and clinical psychopharmacology23(1), 1–21. doi:10.1037/a0038550
  8. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  9. Mendez, M. F., Clark, D. L., Boutros, N. N. (2018). The Brain and Behavior: An Introduction to Behavioral Neuroanatomy. United States: Cambridge University Press.
  10. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biological Psychiatry. 2007.
  11. Papakostas GI. Serotonin norepinephrine reuptake inhibitors: Spectrum of efficacy in major depressive disorder. Primary Psychiatry. 2009;16(Suppl 4):16–24.
  12. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  13. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  14. 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.
  15. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  16. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th Edition.
  17. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Tenth Edition. Philadelphia. Wolters Kluwer. 2017.

 

Helping Someone with Bipolar Disorder – HelpGuide.org

How to support someone during a difficult time

Medication Algorithms for Mental Disorders

How do medications interact to cause side effects?

How do medications interact to cause side effects?

Medications can “interact” in a variety of ways

Here are the most common types of drug-drug interactions (this is not a comprehensive list)

Displacement from transport proteins

Many medications travel in the bloodstream attached to proteins called “transport proteins.” Some medications/drugs might remove or “kick off” a medication from its transport protein.

Altering the activity of metabolic enzymes

Recall that enzymes are like “Pac-Man” that break down (or metabolize) drugs and medications. Some medications alter the activity of the enzymes that metabolize other medications and drugs. If an enzyme’s activity is increased, then the medication metabolized by that enzyme may be metabolized or broken down too quickly. This results in decreased blood levels of the medication which may decrease the medication’s effectiveness. If an enzyme’s activity is decreased, then the medication metabolized by that enzyme may be metabolized or broken down too slowly. This results in increased blood levels of the medication which might cause side effects and toxicity.

Competing for receptors

Some medications might compete with other medications at the same receptor. 

Altering the function of organs like the kidneys, intestines, and liver

Some medications can alter the body’s ability to eliminate drugs and medications. This can occur when one medication alters the functioning of the kidneys, intestines, and/or liver.

Below are the most common drug-drug interactions to be aware of when taking psychotropic medications (i.e., medications used to treat mental disorders)

Valproic acid (VPA, Depakote) + Lamotrigine (Lamictal)

  • Valproic acid (VPA) increases lamotrigine levels by decreasing lamotrigine metabolism
  • Increased lamotrigine levels increase the risk of developing a severe rash
  • Increased lamotrigine levels increase the risk of Steven-Johnson’s Syndrome (SJS/TEN)
  • When taking both valproic acid (Depakote) and lamotrigine (Lamictal), the general recommendation is to decrease the dose of lamotrigine by 50%

Carbamazepine (CBZ) is an inducer of CYP3A4

  • CBZ induces its own metabolism by increasing the activity of the CYP3A4 enzyme
  • CBZ also induces the metabolism of other medications that are metabolized by CYP3A4 such as oral contraceptives, clozapine, alprazolam, buspirone, and clonazepam

Lithium levels are INCREASED when combined with the following

  • Non-Steroid Anti-inflammatory Drugs (NSAIDs), except aspirin
  • Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)
  • Thiazide diuretics such as hydrochlorothiazide
  • Low sodium diets

Lithium levels are DECREASED when combined with the following

  • Caffeine
  • Theophylline
  • High sodium diets

Grapefruit Juice

  • Grapefruit juice is a potent inhibitor of CYP3A4 and P-glycoprotein (another protein that helps eliminate drugs)
  • Therefore, grapefruit juice increases blood levels of many medications metabolized by CYP3A4

Smoking Tobacco cigarettes

  • The hydrocarbons in the smoke of tobacco cigarettes, but not nicotine, increase the activity of CYP1A2 enzymes
  • Smoking cigarettes decreases blood levels of medications metabolized by CYP1A2 such as Olanzapine, Clozapine, and Caffeine

Tyramine + Monoamine Oxidase Inhibitors (MAOIs)

  • Tyramine (TIE-ruh-meen) is an amino acid that occurs naturally in the body and aids in regulating blood pressure. Elevated tyramine levels can lead to dangerously elevated blood pressures.
  • Tyramine is also found in certain foods such as banana peel, beer, fava beans, aged cheese, sauerkraut, sausage, soy sauce, and concentrated yeast extract.
  • An enzyme called monoamine oxidase (MAO) breaks down excess tyramine in the body. Monoamine oxidase inhibitors (MAOIs) are used to treat depression.
  • If taking a monoamine oxidase inhibitor, it is important to avoid certain foods high in tyramine.

Monoamine Oxidase Inhibitors (MAOIs)

  • Monoamine oxidase (MAO) is an enzyme that breaks down monoamines such as serotonin, dopamine and norepinephrine. Therefore, monoamine oxidase inhibitors (MAOIs), such as selegiline and phenelzine, are used to treat depression.
  • Combining MAOIs with Selective Serotonin Reuptake Inhibitors (SSRIs), Tricyclic Antidepressants (TCAs), Pseudoephedrine, and Stimulants increases the risk of serotonin toxicity and dangerously high blood pressures

Fluoxetine, Paroxetine, and Bupropion are potent inhibitors of CYP2D6 

  • Drugs like fluoxetine, paroxetine, and bupropion inhibit CYP2D6 enzymes and increase blood levels of other medications metabolized by CYP2D6.
  • Fluoxetine, paroxetine, and bupropion decrease the effectiveness of Tamoxifen and Codeine because Tamoxifen and Codeine require CYP2D6 activity to be effective. 

Antimicrobial-Psychotropic Drug Interactions

  • Antimalarials increase levels of phenothiazines such as chlorpromazine (Thorazine)
  • Azoles increase levels of alprazolam, midazolam, and buspirone
  • Clarithromycin and Erythromycin increase levels of alprazolam, midazolam, carbamazepine, clozapine, and buspirone
  • Quinolones increase levels of clozapine and benzodiazepines (but decreases the effects of benzodiazepines)
  • Isoniazid increases levels of haloperidol and carbamazepine. Isoniazid + disulfiram can cause problems with motor coordination (called ataxia)
  • Isoniazid and Linezolid are weak inhibitors of monoamine oxidase (MAO) and therefore increases the risk of serotonin syndrome and hypertensive emergencies if used with serotonergic drugs (like SSRIs, SNRIs, and TCAs)

Erythromycin, Clarithromycin, and Ketoconazole + Tricyclic Antidepressants or antipsychotics

  • Combining Erythromycin, Clarithromycin, or Ketoconazole with Tricyclic Antidepressants or antipsychotics increases the risk of QT prolongation and cardiac (ventricular) arrythmias

Drug-Drug Interaction Tables

 

A 5-minute exercise to relieve anxiety and stress

FEELING ANXIOUS?

Try this mindfulness exercise whenever you’re feeling anxious or stressed

Play Video

What is Ketamine? How does it work?

What is Ketamine?

Ketamine is a drug/medication that was initially developed in 1962 as a structurally related alternative to phencyclidine (PCP). At that time, phencyclidine (PCP) was being used as a dissociative anesthetic for humans and animals, but its use was discontinued because of concerns about neurotoxicity.

comparing the structures of ketamine and pcp

Interestingly, ketamine and PCP demonstrated similar anesthetic properties, but ketamine was better tolerated and not neurotoxic at anesthetic doses. This resulted in ketamine’s approval as an anesthetic agent by the U.S. Food and Drug Administration (FDA) in 1970.

Ketamine is abused as a recreational drug and goes by many street names including Barry Farrell, Blind Squid, Cat Food, Cat Valium, Donkey; Green, Honey Oil, Jet, Keller, Kelly’s Day, Ket, Kit Kat, Kitty Flip, Purple, Special La Coke, Super Acid, Super C, Vitamin K, Wobble, Wonk, or simply the letter K.

Can it be used for depression?

Yes, ketamine is a fast-acting antidepressant medication and some patients see improvements in mood within hours to days (rather than weeks or months for classic antidepressants). Ketamine appears to rapidly decrease thoughts of suicide as well. However, the effects are often short-lived. Ketamine by mouth, nasal spray, or intravenous infusion are viable options for those suffering with treatment-resistant depression.

Can it be used for anxiety?

Yes, ketamine has been shown to be effective for people with generalized anxiety, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). A study published in the American Journal of Psychiatry found that repeated doses of ketamine can help reduce the symptoms of people who suffer from PTSD. Over a two-week period, patients received six infusions of ketamine.

Can ketamine be used for alcoholism and other substance use disorders?

Yes, studies have looked into ketamine’s effect on depressed people who have a family history of alcoholism. In research that appeared in the American Journal of Psychiatry, people with problem drinking were administered ketamine along with motivational enhancement therapy, compared with a control group, the ketamine plus therapy group drank less and did not relapse as much.

What is ketamine used to treat?

Ketamine has demonstrated efficacy for the following conditions:

  • Depression
  • Anxiety
  • Obsessive Compulsive Disorder (OCD)
  • Post-Traumatic Stress Disorder (PTSD)
  • Alcohol Use Disorder
  • Chronic Pain

How is Ketamine administered?

Ketamine may be administered in oral form (as a troche/lozenge), through the nose (esketamine nasal spray), or by infusions (intravenously) in specialized clinics. A round of ketamine infusions typically comprises six (6) sessions spread over a two to three weeks and may cost several thousand dollars. Patients typically pay out-of-pocket for ketamine therapy except for the nasal spray, which has an FDA indication for treatment resistant depression. Some patients benefit from the oral form of ketamine, which is much less expensive but requires using a compounding pharmacy.

What’s the difference between ketamine and esketamine?

Ketamine itself is a mixture of two compounds, (R)-Ketamine and (S)-Ketamine. These are called stereoisomers. In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms but differ in the three-dimensional orientations of their atoms in space. By definition, molecules that are stereoisomers of each other represent the same structural isomer.

Ketamine itself is not FDA-approved to treat depression, but the stereoisomer S-ketamine, or esketamine, is. The drug is delivered by nasal spray and is designed to be administered alongside a traditional antidepressant. It was approved specifically for treatment-resistant depression, or depression that has failed to respond to other antidepressant medications.

Is ketamine covered by insurance?

Because esketamine, but not ketamine, is FDA-approved, it may be covered by insurance. But the drug must be administered under a doctor’s supervision, which limits its availability/accessibility. 

What are the side effects of ketamine?

Side effects of ketamine can include

  • Dissociation
  • Dizziness
  • Anxiety
  • Nausea
  • Numbness
  • Sedation
  • Vertigo
  • Lethargy
  • Hallucinations
  • Blood pressure elevations
  • Induction of mania/hypomania

Ketamine is toxic to the lining of the bladder and may cause inflammation of the bladder–called ulcerative cystitis.

How does ketamine work? What is the mechanism of action underlying ketamine’s antidepressant effects?

Ketamine’s antidepressant effects are changing our understanding of the neurobiology of depression. While it remains unclear exactly how ketamine relieves depression, there are different ways to look at ketamine’s therapeutic effects. 

  1. Experiential Effects
  2. Biochemical/Pharmacological Effects 

Experiential Effects

Ketamine induces a dissociative state. That is, people feel as though their minds have detached from their bodies. Initially, this can be terrifying because of the loss of control. Over the course of multiple infusions, people learn to “let go” of that control and become detached observers of their experiences. As a result, many will report discomfort during the first few infusions. Invariably, a shift occurs, and the experience becomes more pleasant and peaceful.

I recall multiple patients reporting back to me how they felt a renewed sense of optimism and hope after their ketamine experiences. 

For most people, the rapid antidepressant effects of ketamine do not last longer than a few weeks to months. However, if used appropriately in conjunction with psychotherapy and lifestyle changes, ketamine can be an effective way to overcome the initial “hump” that keeps people stuck in repetitive patterns of thoughts and behaviors. In a way, ketamine is like the fast-acting “behavioral activator.” 

Biochemical/Pharmacological Effects

Ketamine affects multiple neurotransmitter systems—including the opioid system, monoaminergic (i.e., norepinephrine, serotonin, dopamine) systems, glutamatergic system, and the muscarinic (cholinergic) system to name a few—but the leading theories for how ketamine works as an antidepressant implicate the glutamatergic (glutamate) system.

Below is a video explaining the proposed pharmacological mechanism of action of ketamine.

Watch the video below before continuing. 

As illustrated in the video, Ketamine’s primary mechanism of action is antagonism, or blockade, of N-methyl-d-aspartate (NMDA) receptors.

N-methyl-d-aspartate (NMDA) receptors are glutamate receptors (glutamate binds and activates NMDA receptors on neurons). NMDA receptors work together with AMPA receptors, another type of glutamate receptor, to initiate changes within neurons. These changes include increased survival, viability, and stronger connections with other neurons.  

NMDA receptors are the primary targets for both ketamine and PCP. Interestingly, NMDA receptors are also targets for medications such as Memantine (Namenda), a medication for Alzheimer’s Dementia, and Dextromethorphan, the active ingredient in Robitussin. It isn’t surprising that both of these medications are now being investigated for depression.

Skolnick and colleagues (1996) first postulated a role for the glutamate system in depression when they noted that drugs that block NMDA receptors mimicked the effects of clinically effective antidepressants.

The leading hypothesis is that the initial effects at NMDA and AMPA receptors modulate cellular and molecular processes that are known to be important mediators in the formation of new and “stronger” neuronal connections–a concept termed neuroplasticity. This is the primary molecular mechanism for learning and memory. 

Normally, glutamate stimulates both NMDA and AMPA receptors. Activation of BOTH these receptors “tells” the neuron to produce important proteins involved in cell growth and survival. Although both NMDA and AMPA receptors must be activated together for this to occur, it appears that AMPA receptors are most important. That is, when only NMDA receptors are activated and AMPA receptors are blocked, these changes don’t occur (see figure below).

Selectively blocking NMDA receptors with ketamine means there is more glutamate available to activate AMPA receptors. Increased activation of AMPA receptors hastens AMPA-mediated changes in the cell such as production of more AMPA receptors and production of growth factors to name a few. These changes ultimately strengthen the connection between neurons and produce more connections (see figure below). While this is a simplified explanation (it is much more complicated than this) it provides a basic understanding of how we think Ketamine works as an antidepressant. 

In summary, ketamine’s downstream effects include upregulation of important growth factor proteins such as mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (EEF-2), glycogen synthase kinase 3 (GSK-3), and brain-derived neurotrophic factor (BDNF) that increase neuronal cell growth, survival, and formation of new connections. It is important to mention that the precise mechanisms implicated in the antidepressant response to ketamine remains unknown and is likely multifactorial.

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References

  1. Ebenezer, Ivor. Neuropsychopharmacology and Therapeutics. John Wiley & Sons, Ltd. 2015.
  2. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  3. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  4. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  5. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  6. Purves, D., et al. (2018) Neuroscience. 6th Edition, Sinauer Associates, New York.
  7. Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). New York, NY, US: Cambridge University Press.
  8. Meyer, Jerrold, and Quenzer, Linda. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates. 2018.
For more information about ketamine, ketamine-assisted therapy, and ketamine infusions, visit the following links:

How To Escape the Mind Prison: A Guide

HOW TO ESCAPE THE MIND PRISON: A GUIDE 

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