The pharmacodynamics of Isocarboxazid


After reviewing the material presented in this case study, there are some concerning questions regarding this patient’s psychiatric history. Additional questions would include:

After each discontinuation of medication after an episode of depression, was this decision the choice of a physician or self -initiated? This question would provide knowledge of the patient’s medication compliance. For example, does the patient stop taking prescribed medication on symptoms are alleviated?

What were the circumstances prior to each depressive episode? his question would enlighten the practitioner on triggers and factors that personally affect the patient before a depressive episode occurs.

There appears to be history of alcohol abuse and depression in your family, has anyone in your family received treatment? This question would provide a view into the patient’s understanding of psychiatric treatment. Since the patient does not believe in psychotherapy due to religious reason, the patient may not know what treatments were, are or will be available to him.

Feedback from People in Patient’s Life

The patient has been married for 33 years. Assuming his spouse is around before, during and after an episode, she may provide information the patient failed to share or may not have been honest about. The first person to be questioned would be the patient’s wife. Some of the questions for the patient’s wife would include onset of symptoms. What occurs before each episode of depression? Is there conflict between you and your spouse? Are there any stressors, such as financial plaguing your spouse and you?

The patient also has three children. All three of his children suffer from some form of depression. Questioning the patient’s children may provide a historical history of the patient. For example, the children may have noticed symptoms leading to the patient’s depression years ago. Questions for the children may include did your parent’s argue often while you were growing up? Did your father ever lose interest in your childhood years? Did you feel love or rejection while growing up from your father? What were your father’s behaviors? Did you ever notice any alcohol or drug abuse while growing up?

Physical and Diagnostic Exams for Patient

Unfortunately, there is not a certain test for depression. The primary goal of physical exam and diagnostic testing would to rule out other conditions causing similar symptoms. A physical exam should be preformed assessing respiratory and cardiovascular system. Vital signs should be taken as well.

Certain labs should be assessed in the patient. The practitioner should check the patient’s thyroid levels. Thyroid hormones have been linked to depression (Stahl, 2008). Depression can be caused by an underactive or overactive thyroid.

Another lab test to consider would be dexamethasone suppression test. This test assesses the negative affect of dexamethasone. Once given dexamethasone, in a small dose, cortisol levels are decreased in healthy adults, but may remain elevated in depressed patients (Smith, et al., 2013).

Depressive disorders have been linked to certain inflammatory biomarkers. This blood test assesses nine biomarkers, alpha-1 antitrypsin, apolipoprotein CIII, BDNF, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resin, and soluble tumor necrosis factor α type II. These biomarkers represent the inflammatory and metabolic pathways associated with depression (Serra et al., 2015).

Three Differential Diagnosis

Based on the symptoms listed by the patient, there a multiple diagnosis this patient could be suffering from. Recurrent Major Depressive Disorder with melancholic features. This diagnosis is due to the patient’s major depressive symptoms, such as depressed mood most of the day, increased anxiety, and suicidal thoughts (Zaninotto et al., 2016). The specifier of melancholic features is based on the patient’s symptoms being worse in the morning, inability to function and lack of pleasure (Zaninotto et al., 2016). Other diagnoses for the is patient could be a thyroid imbalance or panic disorder

Two pharmacologic agents

Since this patient has become resistant to first line and second line drug therapy for depression, Phenelzine, an MAOI should be started for this patient. Phenelzine 45mg daily, divided into three doses throughout the day.  Another suggestion for this patient would be Isocarboxazid. The dosage would start at 10mg BID, if tolerated the dosage could increase to another 10mg every 2-4 days until the dosage of 40 mg was achieved with tolerance. If therapeutic response is achieved, this medication should be slowly decreased without affecting therapeutic response (Arcangelo et al., 2013). Due to the pharmacokinetics and pharmacodynamics of Isocarboxazid, Phenelzine, should be prescribed to this patient. Since there is an increased to patients who have cardiac issues such as atrial fibrillation. The pharmacodynamics of Isocarboxazid are not clearly understood, but this may be due to the inhibition of MAO to the heart (Drugs, 2018).

MAOIs and Ethnicities

With many MAOIs, hypertensive crisis is a major concern for nay race. Since minorities are diagnosed with hypertension at higher rates, this causes a greater concern. This is the reason for a tyramine restricted diet.  Foods such as aged chees, yeast and tap beer should be avoided ()

Changes in Therapy

After review of further data with this patient, changes would not be made to the suggested treatment.

Lessons Learned

Throughout this case study many lessons were present.  The lesson of medication compliance was the first lesson learned. Another lesson learned was the lesson of proper medication selection in a patient, especially after a recurrent episode of depression.  Assessment and presentation of psychiatric treatment for patients was another lesson learned from this case study.


In conclusion, this case study involved a 63-year-old male with recurrent depression. The patient has had success and failures with medication and treatment. These failures may be due to medication compliance or improper cessation of medications from a physician. After two years, the patient is finally on the right track. Hopefully, this will continue.


Arcangelo, V. P., Peterson, A. M., Wilbur, V., & Reinhold, J. A. (Eds.). (2017). Pharmacotherapeutics for advanced practice: A practical approach (4th ed.). Ambler, PA: Lippincott Williams & Wilkins. (2018).  Isocarboxazid. Retrieved from http:/ ttps://

Serra, F., Spoto, A., Ghisi, M., & Vidotto, G. (2015). Formal Psychological Assessment in Evaluating Depression: A New Methodology to Build Exhaustive and Irredundant Adaptive Questionnaires. PLoS ONE10(4), e0122131.

Smith, K. M., Renshaw, P. F., & Bilello, J. (2013). The diagnosis of depression: current and emerging methods. Comprehensive Psychiatry54(1), 1–6.

Stahl, S. M. (2008). Essential Psychopharmacology Online. Retrieved September 11, 2018 from

Zaninotto, L., Solmi, M., Veronese, N., Guglielmo, R., Ioime, L., Camardese, G., & Serretti, A. (2016). A meta-analysis of cognitive performance in melancholic versus non-melancholic unipolar depression. Journal of affective disorders201, 15-24.


Three questions that I might ask our patient are:

  1. Tell me when you take your medication? [The reason for this question is to establish his adherence to his medication. Tachyphylaxis aka poop out, may occur due to medication nonadherence. It is therefore important to assess if the client is experiencing tachyphylaxis related to medication nonadherence] (Targum, 2014).
  2. Do you feel a lack of motivation about life? [The Rothschild Scale for Antidepressant Tachyphylaxis suggests a conceptualization of antidepressant tachyphylaxis that is characterized by symptoms of apathy.] (Targum, 2014).
  3. Are you experiencing patterns of sleep disturbance? [This is also a symptom of poop out. It is important to assess these symptoms in order to proceed with his plan of care. Another important question is to assess the client for is substance abuse which was already addressed within the case study.)

According to our case study, our client is a 69-year-old retired male who is married with children and grandchildren. In my opinion, it would be most important to speak to those that are the closest to him (his wife) who can observe him for any signs of activation of bipolar disorder such as: lack of impulse control, irritable and agitated mood lasting longer than a week (Bail, Dains, Flynn, Solomon, & Stewart, 2015). Activation of bipolar disorder would require his antidepressant to be discontinued and switched to a mood stabilizer (Stahl, 2013).

Physical exams and diagnostic tests relevant to our client’s care would be testing his blood pressure before/during initiating treatment and testing for plasma levels of O-desmethylvenlafaxine (ODV) which is an active metabolite of venlafaxine formed as a result of CYP450 2D6 (Stahl, 2013). Plasma levels of ODV will determine if the provider may safely increase his dose based on results. It is imperative to assess our client’s blood pressure related to the effects of the norepinephrine in the SNRI. Based on the check points for his first follow up, I would have changed his phone follow up to a face to face follow up to assess our client better and would have ordered his plasma ODV sooner to properly assess the effectiveness of his medication therapy.

According to the American Psychiatric Association (2013), three differential diagnoses that I am giving our client are: 1. mood disorder due to another medical condition 2. Sadness 3. Adjustment disorder with depressed mood. The one that I think is more likely is sadness. My thought is sadness because our client’s history from the case study reveals a long, waxing and waning major depressive episode where he feels like he is out of options (Stahl, 2013).

Two pharmacologic agents that would be appropriate for our client’s therapy would be Mirtazapine 15 mg PO nightly or Bupropion 75 mg PO BID. Bupropion is an NDRI which is a good augmenting combination with Venlafaxine. It is a powerful enhancer of noradrenergic action. Mirtazapine is a dual serotonin and norepinephrine combination which also works well with Venlafaxine but it may further increase his high cholesterol; for this reason, I would choose the Bupropion.

Lessons that I learned from this case study are certain drugs may not be as effective due to noncompliance, pharmacokinetic failures or even genetic variants. I have also learned the seriousness of how severe depression can be and the importance of knowing not necessarily all of the drugs out on the market for depression but more so the pharmacokinetics and pharmacodynamics of how they work.



Targum, S. D. (2014). Identification and treatment of antidepressant tachyphylaxis. Innovations in Clinical Neuroscience, 11(24), 3-4. Retrieved from

Ball, J. W., Dains, J. E., Flynn, J. A., Solomon, B. S., & Stewart, R. W. (2015). Seidel’s guide to     physical examination (8th ed.). St. Louis, MO: Elsevier Mosby.

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. Retrieved from Walden Library databases.

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