The Case # 1: The man whose antidepressants stopped working

The 63 yr-old with the worst depression and anxiety he has ever felt.  He is married for 33 years and with 3 children.  He is a non-smoker and non-drug and alcohol abuse.  He has a medical history of Atrial fibrillation and Hypercholesterolemia.  He has a family history with depression that is the mother, son, and daughter.

Three Questions I might ask the patient if he were in my office.

  1. What is your current problem, symptoms, and thoughts?
  2. What are your interpersonal or psychosocial stressors?

Rationale:  The goal is to learn more about the patient, his current problems and symptoms; a complete history of previous symptoms; a family history; a history of significant stressful life events (psychosocial stressors); information concerning lifestyle, culture, social support structure and any suicidal thoughts or tendencies the person may be experiencing.

  1. Are you comfortable if we can involve your family members or significant other in psychoeducation and treatment?

Rationale:  According to Gulf Bend Center (n.d.a.) one of the well-studied sociological factors that helps prevent depression is known as “social support.”  Social support simply refers to whether or not people have access to and make use of a network of interpersonal relationships for supportive purposes.  People receive social support from their family, friends, work, and significant others.  Social support networks provide a shoulder, guidance, love, caring, entertainment, laughs, and other types of mental and physical assistance during times of need and crisis.

  1. For your recurrence depression, can we try a combination of medication and psychotherapy?

Rationale:  Psychotherapy has been recommended for the treatment of depression which

includes cognitive-behavioral therapy (CBT), interpersonal psychotherapy, and problem-solving therapy.  CBT is considered as the first-line and most evidence-based psychological therapy for depression.  CBT works by identifying any dysfunctional thoughts and replacing them with more helpful ones, with the intent of modifying negative behaviors and emotions that perpetuate the depression (Ng, How & Ng, 2017).

Physical Exams and diagnostic tests appropriate for the patient and how the result would be used.

Although his vital signs are normal where we have BP normal, BMI normal and normal fasting glucose and triglycerides it is very important to do lab measurements and to screen for thyroid dysfunction and dexamethasone suppression test.  According to Samuels (2018), it should be a routine clinical practice to screen patients with depression for thyroid dysfunction.  Many patients with depression who are screened for thyroid dysfunction have mildly elevated thyrotropin (TSH) and normal free thyroxine (T4) levels (mild or subclinical hypothyroidism).  The patient and care provider may attribute the depressive symptoms to mild thyroid disorder and initiate L-T4 therapy.  Also, a complete diagnostic evaluation for depression should include tests for bacterial and viral infections, metabolic deficiencies, and autoimmune conditions.

Depressive symptoms are sometimes measured with general questionnaires designed to look at several different types of mental conditions as once.  The general health questionnaire (GHQ) is a screening test for identifying minor psychiatric disorders in the general population.  It looks at the person’s current state and asks if that is different from the usual state.  It is sensitive to short-term psychiatric disorders, but not to long-standing characteristics of the person.  This self-administered questionnaire focuses on two major areas: the inability to function in daily life and the appearance of new and distressing symptoms (Gulf Bend Center, n.d.a.)

Three differential diagnoses for the patient: Identify one that is most likely diagnoses.

According to the criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (n.d.a.) and using the screening tools, the diagnosis established would be Major Depressive Disorder (MDD) where the clinician needs to differentiate and identify other conditions that may have similar symptoms.  This will help to provide information about a person’s anticipated course of the disorder and their prognosis (outcome).

The clinician may use the following differential diagnosis to describe the current or most recent Major Depressive Disorder:

  1. Mood disorder due to another medical condition.
  2. Adjustment disorder with depressed mood.
  3. Melancholic Features

The most likely diagnosis of the 63 yrs-old is MDD with melancholic features that have been described by the most severe stages of his five (5) episodes which include:

  • An inability to enjoy anything and does not react to anything pleasurable along with a mood that      is regularly worse in the morning.
  • Early morning awakening (at least two hours before the usual time)
  • Thinking of moving slowly.
  • Significant loss of appetite or unplanned weight loss.
  • Excessive or inappropriate guilt.

Two pharmacologic agents and their dosing that would be appropriate for the patient’s antidepressant therapy.

According to Stahl’s (2013) adults between the ages of 25 and 64 might have the best chance of getting a good response and with the best tolerability to an antidepressant.  In his fourth episode, he was prescribed venlafaxine XR (Effexor XR) which worked even faster as compared with the other antidepressants and the patient did not have sexual dysfunction but discontinued after less than a year.  This was a major mistake to discontinue the medication because he already had a family history and recurrent episodes of depression.  Venlafaxine XR is a Norepinephrine and dopamine reuptake inhibitors (NDRIs) work in the same way as the other neurotransmitter reuptake inhibitors.  NDRIs Venlafaxine frequently seems to have greater antidepressant efficacy as the dose increases theoretically due to recruiting more and more Norepinephrine transporter (NET) inhibition as the dose is raised.

After the fifth episode after taking Venlafaxine XR for 15 months there was no relief of the symptoms which can be a result of the patient had become resistant and as his age progresses to 63 yrs-old also the changes in brain structure and neurotrophic factors.  Due to recurrent, and recurrences of depression which possibly indicate disease progression potentially manifested as shorter and shorter periods of wellness between subsequent episodes, which has resulted to poor inter episode recovery and ultimately, treatment resistance thus the need to introduce tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) which are regarded as second-line and third-line due to their tolerability and safety profile.  Tricyclic antidepressants have antagonist action at 5HT2A and 5HT2C which could contribute to their therapeutic profile.  Monoamine oxidase inhibitors (MAOIs) are enzymes that break down serotonin, norepinephrine, and dopamine.  By preventing these enzymes from working MAOI medications allow neurotransmitters to remain the synaptic gap longer thus giving more opportunity to activate the post-synaptic neuron’s receptor and create greater stimulation of the post-synaptic recipient neuron.  Increasing serotonin, norepinephrine and dopamine levels tend to have an antidepressant effect.  There is no contraindication to use as a treatment for depression due to the patient ethnicity although TCAs can cause anticholinergic effects (dry eyes, constipation, and urinary hesitancy) and be lethal if overdosed.  MAOIs can lead to a hypertensive crisis if combined with tyramine-rich foods such as cheese and many medications, including common primary care drugs such as decongestants and cough syrups (Stahl’s, 2013).

As a clinician, when prescribing treatment for depression patients may have to try several different medications before finding one that works well.  Even within a group of similar antidepressant medications, some people do better with one than with others.  The decision about when it is time to try new medications is best made when the patient, clinician and psychotherapist work together as a team.  For this patient, I believe the combination of psychotherapy and medication would have been beneficial and probably he would have been able to get to a point where he could gradually decrease or discontinue the use of antidepressants.  He would have learned how to maintain well-being by using skills learned in psychotherapy.  However, for those individuals whose depression returns when they stop using the medication, long-term use of antidepressants may be necessary.


Diagnostic and Statistical Manual of Mental Disorders (DSM-5)(n.d.a.). Retrieved on March 11th, 2020 from

Gulf Bend Center (n.d.a.). Depression: Depression & related conditions basic information. Retrieved on March 11th, 2020 from

Ng, C. W. M., How, C. H., & Ng, Y. P. (2017). Managing depression in primary care. Singapore Med J. 58(8), 459-466,

Samuels, M. H. (2018). Subclinical hypothyroidism and depression: Is there a link? The Journal of Clinical Endocrinology & Metabolism. 103(5), 2061-2064,

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

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