Week 3 Discussion
Case 3: Volume 1, Case #29
The depressed man who thought he was out of options.
The patient is a 69 year old male with unremitting chronic depression. He has suffered from depressive episodes for 40 years and has always had a good response to treatment until 5 years ago when he relapsed on venlafaxine. Two years ago he underwent nine treatments of ECT with partial response. He has tried every known antidepressant and augmentation available in the past few years.
The patient should be asked about recent stressful life events, consumption of illicit drugs, alcohol abuse, current medical conditions and prescribed medications (Preda, 2018). If the patient was in my office, I would also want to ask questions to gain an understanding of the severity of his depression. It is important to assess the overall severity of depression symptoms because symptom severity corelates with suicide risk (Preda, 2018). The PHQ-9 screening could be used and this screening asks about feelings of hopelessness, loss of pleasure in doing things, and feelings of being better off dead. A focused severity assessment for hopelessness, suicidal ideation, and psychotic symptoms is recommended; these symptoms independently increase the risk for suicide (Preda, 2018). This patient reports feeling severely depressed and demoralized, as well as, helplessness, hopelessness, and worthlessness. His depression is the worst it has ever been.
Family members are helpful informants, can ensure medication compliance, and can encourage patients to change behaviors that perpetuate depression (eg, inactivity) (Halverson, 2019). Some questions I would ask family members would include whether or not the patient is taking their medication and I would ask the family to provide some insight as to how the patient behaves at home. The wife reports that she feels he is letting go and giving up.
There are no lab tests that will confirm depressive disorder; however, labs can be ordered to rule out illnesses that may present as depressive disorder such as endocrinological or neurological diseases. Labs tests may include TSH, B12, RPR, HIV test, electrolytes, BUN and creatinine, blood alcohol, and blood and urine toxicology screening. Neuroimaging can help clarify the nature of the neurologic illness that may produce psychiatric symptoms, but these studies are costly and may be of questionable value in patients without discrete neurologic deficits (Halverson, 2019). CT scanning or MRI of the brain should be ordered for suspected organic brain syndrome. PET scans provide a means for studying receptor binding of certain ligands and the effect a compound may have on receptors (Halverson, 2019).
Differential diagnosis would include major depressive disorder, bipolar disorder, and/or poor or rapid metabolism. From 25-50% of cases of Treatment Resistant Depression (TRD) are associated with bipolar disorder; this is by far the most common individual cause of TRD (Preda, 2018). The remaining 50-75% are associated with noncompliance, poor or rapid metabolism, or misdiagnosis (Preda, 2018). This patient is exhibiting signs and symptoms consistent with major depressive disorder, such as anhedonia, loss of energy, feelings of worthlessness, depressed mood, which have been consistent for more than a two week period. TRD is defined as MDD that fails to respond to at least two antidepressant trials that are of adequate dose and duration; the two antidepressants may belong either to the same class or to different classes (Preda, 2018). Differential diagnoses include major depression, bipolar disorder, and/or slow or rapid metabolism. Bipolar disorder is associated with 25-50% of cases of Treatment Resistant Depression (TRD); this is by far the most common individual cause of TRD (Preda, 2018). The remaining 50-75% are due to noncompliance, slow or fast metabolism, or misdiagnosis (Preda, 2018). This patient has been exhibiting signs and symptoms consistent with major depressive disorder, such as anhedonia, loss of energy, feelings of worthlessness, and depressed mood, for more than two weeks. TRD is defined as MDD that does not respond to at least two adequate dose and duration antidepressant trials; the two antidepressants may be from the same or different classes (Preda, 2018).
SSRIs, which include fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine, have become the first-line treatment for major depression (Brown, 2011). SSRIs work by selectively blocking the reuptake of serotonin to increase the amount of serotonin available in synapses in the brain (Brown, 2011). The STAR*D trial examined various strategies for treatment resistant depression in patients who did not respond to an initial SSRI, including switching to another SSRI antidepressant, changing medication class, and switching to CBT. Fair quality studies have indicated a trend toward greater effectiveness when switching to an SNRI such as venlafaxine than with citalopram, fluoxetine, or paroxetine (Halverson, 2019).
For patients with major depressive disorder, I would start the patient on citalopram 20mg and increase the dose to a maximum of 40mg. If the patient failed to respond, I would change to venlafaxine 75mg daily extended release tablet and increase dose if tolerated. I could not find any contraindications or dosing alterations needed for Citalopram or venlafaxine related to ethnicity.
Week 20 follow-up concluded with ordering venlafaxine levels. This had been considered 20 weeks prior. I agree with ordering this lab and I would have opted to do this before pursuing ECT. A lab is much less invasive, less expensive, and without the side effects he is experiencing at this point.
The patients aphasia and mood are improving but his mood is still low. He hadn’t had labs completed. The venlafaxine stayed at 225mg and aripiprazole was increased. Aripiprazole was increased to 15mg. When used to augment treatment with an SSRI or SNRI for depression, the dose would be no greater than 10mg. I disagree with this change.
By week 28 the patient labs show low levels of venlafaxine on a 225mg dose. The dose was increased to 300mg. Up to 600mg/day has been given for heroic cases (Stahl, 2014). I agree with this change. His aripiprazole was discontinued. I agree with discontinuing since the venlafaxine was not at a therapeutic level.
The patient was still not showing improvement by week 32. Another blood level was drawn. At week 36, the level was low on a 300mg dose. The dose was increased to 375mg. The patients BP is good and there have not been any side effects. He has shown some improvement after the dose increase. An increase to 450mg was made and levels ordered. By week 40, the patient was feeling hopeful and mood was improving. His lab values were in the low therapeutic range. At 450mg/day, the patient was still within the dosage for a heroic case. He was tolerating well. The suggestion at this point was to raise dose by 75mg/day, redraw level and raise again to 600mg if still in therapeutic range. I think this is a good strategy based on the patients improvement and his ability to tolerate the dose. Lessons learned include the importance of therapeutic drug level monitoring when this is an option. Possible reasons for low levels could be: pharmacokinetic failure, genetic variant causing pharmacokinetic failure, or noncompliance. Last but not least, never give up.
References
Bienenfeld, David. (2018). Screening tests for depression. Medscape. Retrieved from https://emedicine.medscape.com/article/1859039-overview
Brown, Charles. (2011). Pharmacotherapy of major depressive disorder. US Pharmacist, 36(11), HS3-HS8. Retrieved from https://www.uspharmacist.com/article/pharmacotherapy-of-major-depressive-disorder
Halverson, Jerry. (2019). Depression. Medscape. Retrieved from https://emedicine.medscape.com/article/286759-overview
Howland, R. H. (2008a). Sequenced treatment alternatives to relieve depression (STAR*D). Part 2: Study outcomes. Journal of Psychosocial Nursing and Mental Health Services, 46(19), 21–24. doi:10.3928/02793695-20081001-05. Retrieved from Walden Library databases.
Howland, R. H. (2008a). Sequenced treatment alternatives to relieve depression (STAR*D). Part 1: Study design. Journal of Psychosocial Nursing and Mental Health Services, 46(9), 21–24. doi:10.3928/02793695-20080901-06. Retrieved from Walden Library databases.
Preda, Adrian. (2018). Major depressive disorder: Disabling and dangerous. Medscape. Retrieved from https://reference.medscape.com/slideshow/major-depressive-disorder-6009734#4
Pigott H. E. (2015). The STAR*D Trial: It Is Time to Reexamine the Clinical Beliefs That Guide the Treatment of Major Depression. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 60(1), 9-13.
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.
Stahl, S. M. (2014b). The prescriber’s guide (5th ed.). New York, NY: Cambridge University Press.
