Individualized antidepressant therapy in patients with major depressive disorder

Case descriptions

Case 1. J.M. is a 59-year-old man seen at your multidisciplinary primary care clinic. J.M. has been newly diagnosed with moderately severe MDD. He is interested in a trial of an antidepressant. J.M. has a history of hypertension, type 2 diabetes mellitus, dyslipidemia, peripheral neuropathy, and obesity. How would you determine the appropriate antidepressant to initiate for J.M.?

Case 2. C.P. is a healthy 32-year-old woman who has just been diagnosed with MDD. You believe that C.P. would benefit from an antidepressant, but C.P. seems unsure. C.P. shares that she has been having troubles with her libido. How would you decide which antidepressant would be most appropriate for C.P.?

Sources of information

A literature review was conducted using Google Scholar, PubMed, the Cochrane Database of Systematic Reviews, and Trip Pro using the following MeSH headings: depression, antidepressive agents, primary care, practice patterns, medication adherence, and decision making, shared. Abstracts of all papers were retrieved and those related to the management of depression in primary care, shared decision making in depression, or antidepressant prescribing patterns in primary care were included in this review. Relevant consensus guidelines or practice statements from the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the Canadian Task Force on Preventive Health Care (CTFPHC) were included. Relevant topics in tertiary databases, such as UpToDate, were retrieved and critiqued, and relevant citations were included in this clinical review.

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Screening. The CTFPHC does not recommend routinely screening for depression in adults who present at primary care settings with no apparent symptoms of depression (weak recommendation).¹² The CTFPHC guideline does suggest that screening may be appropriate if patients present with signs or symptoms of depression or verbalize symptoms of depression.¹² This CTFPHC guideline does not apply to people with known depression, with a history of depression, or who are receiving treatment for depression.¹²

In a meta-analysis of screening instruments in primary care, the median sensitivity and specificity of instruments were 85% and 74%, respectively, with no significant differences in performance between instruments.¹³ The Patient Health Questionnaire–9 (Table 1)¹⁴ is the most commonly used tool for screening for depression in primary care and has been shown to have sensitivity and specificity for depression screening comparable to semistructured interviews in a variety of age ranges and cultures.^15,16 The Patient Health Questionnaire–9 has also been useful for monitoring patient response to treatment.^16,17

Assessment. Diagnosis of MDD is established once a patient meets the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; Box 1).¹⁸ The DSM-5 was introduced in 2013 without changing the MDD core symptoms and duration from the DSM 4th edition, text revision (DSM-IV-TR).^1,18 Notable changes in the DSM-5 include removing the bereavement exclusion from the DSM-IV-TR, adding persistent depressive disorder as a new classification of chronic depression (formerly known as chronic major depressive episode and dysthymic disorder in the DSM-IV-TR), and adding 2 new depressive disorders: disruptive mood dysregulation disorder and premenstrual dysphoric disorder.^1,18

Management. Options for depression management include pharmacologic therapy, psychotherapy, neurostimulatory therapy, lifestyle modifications, complementary or alternative therapies, or a combination of various therapies.¹ This review focuses solely on pharmacologic therapy. The most recent CANMAT guidelines on MDD (published in 2016) recommend 15 different antidepressants as possible first-line therapy (Table 2).¹⁹ A 2018 systematic review and network meta-analysis did not demonstrate statistically significant superiority of any particular first-line antidepressant.⁸ The CANMAT depression guidelines provide a list of patient and medication factors to consider when selecting from the many antidepressant drugs recommended for MDD treatment.¹⁹ Patient factors include clinical features and dimensions, comorbid conditions, response and side effects during previous use of antidepressants, and patient preference. Medication factors to consider include comparative efficacy, comparative tolerability, potential drug interactions, simplicity of use, cost, and availability.¹⁹ There are limited tools and support available to help primary care prescribers tailor antidepressants based on medication and patient factors.²⁰

Our proposed Antidepressant Decision Support Tool (Figures 1A and 1B; references are provided in Appendix 1, available from CFPlus*) was developed to assist prescribers and adult patients in selecting an individualized and optimal first-line antidepressant medication for acute MDD treatment. Once a patient is diagnosed with MDD and pharmacologic therapy is part of the elected treatment modality, prescribers can use the Antidepressant Decision Support Tool to select an antidepressant with their patient. The tool’s algorithm starts in the top left-hand corner of Figure 1A. The prescriber determines whether the patient has any MDD specifiers as defined by the DSM-5.¹⁸ If the patient is diagnosed with a MDD specifier, stage 1 of the tool guides the prescriber to a horizontal box labeled Depression specifiers at the top of Figure 1A. The Depression specifiers box contains summarized antidepressant recommendations from the most recent CANMAT guidelines for treatment of the respective MDD specifier. If the patient is not diagnosed with an MDD specifier, the Antidepressant Decision Support Tool stage 1 guides the prescriber to the box labeled No depression specifiers. On the left-hand side of Figure 1A in the No depression specifiers box, the tool starts with consideration of the patient’s comorbidities; if the patient has no comorbidities, any first-line agent may be selected and prescribers can move to stage 2 (Figure 1B) of the Antidepressant Decision Support Tool to narrow down antidepressant choices. For patients with comorbidities, considerations are organized according to the affected system of the body. Antidepressants with published evidence supporting their use in association with a particular comorbidity are summarized in the No depression specifiers box (Figure 1A).

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Figure 1A.

Antidepressant Decision Support Tool: Stage 1—adult depression antidepressant treatment based on efficacy and comorbidities.*

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Figure 1B.

Antidepressant Decision Support Tool: Stage 2—considerations in antidepressant decision making.*

Stage 2 of the tool further assists with individualizing antidepressant therapy. After using stage 1 of the Antidepressant Decision Support Tool, prescribers may have successfully narrowed down antidepressant options based on a patient’s comorbidities but may not have definitively chosen which antidepressive agent to recommend. Stage 2 of the tool uses patient considerations—such as patient preference based on adverse effects, concomitant drug therapy, administration considerations, renal or liver dysfunction considerations, patient preference for specific antidepressants, the patient’s previous antidepressant experiences, and cost considerations—to narrow down antidepressant options further. The ultimate goal of the tool is to support a thoughtful antidepressant choice through patient-prescriber collaboration.

Considering patient characteristics in antidepressant prescribing is not a novel idea. Prescribers already consider a patient’s age, comorbidities, specific depression symptoms, and preferences prior to initiating antidepressant therapy. However, no systematic decision support tools have been published to date that assist prescribers in selecting an antidepressant individualized to the patient. The Antidepressant Decision Support Tool was not meant to replace a prescriber’s clinical decision-making process; rather, it was developed to support prescribers in a comprehensive, evidence-based, and pragmatic evaluation of patient characteristics to tailor antidepressant therapy. The visual tool also allows patient engagement in their own care by giving the patient an opportunity to view and discuss the rationale of antidepressant selection with their prescriber. Shared decision making between clinicians and patients for antidepressant therapy has been shown to improve clinician and patient satisfaction and comfort with treatment decisions.²¹

There is a paucity of evidence demonstrating improved outcomes or improved patient adherence with individualized antidepressant therapy. Studies are currently being conducted to investigate whether individualizing antidepressant therapy improves depression outcomes.²² Antidepressant therapy may not be the most appropriate treatment modality for all patients experiencing MDD. The pilot Antidepressant Decision Support Tool does not include an algorithm to assist patients and prescribers with decisions regarding treatment modality (psychotherapy, pharmacotherapy, lifestyle therapy, or a combination of various modalities); the tool assumes that the prescriber and patient have already decided to pursue pharmacotherapy.

The pilot Antidepressant Decision Support Tool focuses solely on pharmacologic management of depression in adults based on current evidence. Once the utility of the decision support tool is established, future projects include expanding evidence-based algorithms for switching antidepressants, adding details about using augmenting agents in conjunction with antidepressants, expanding the algorithm to include second- and third-line agents, and supporting pharmacologic selection in specific populations such as geriatric patients, women, and adolescents and young adults. To date, studies in these populations are limited and antidepressants are used with precautions in these populations.

Case resolutions

Case 1. J.M. is currently taking 5 mg of rosuvastatin daily, 5 mg of ramipril daily, 1000 mg of metformin twice daily with meals, and 5 mg of linagliptin daily. He has no history of renal or liver disease. You review J.M.’s laboratory results and investigations and find no substantial abnormalities. J.M. states that the peripheral neuropathy in his feet has been bothersome. You find out that J.M. had been diagnosed with depression previously (approximately 20 years ago) and had been prescribed amitriptyline, which caused intolerable side effects. J.M. also shares that he is concerned about weight gain because of his diabetes. J.M. is unemployed and receives social assistance; medication costs are a concern for him. Using the Antidepressant Decision Support Tool, you review the Diabetic peripheral neuropathy section under Comorbidities present in stage 1 (Figure 1A) of the tool and narrow down J.M.’s options to desvenlafaxine, duloxetine, or venlafaxine. Using stage 2 of the tool (Figure 1B), you discover that desvenlafaxine is not covered and may not be affordable for J.M. You and J.M. discuss the options of duloxetine or venlafaxine. J.M. decides he would like to initiate duloxetine. You write him a prescription to start 30 mg of duloxetine daily and to follow up in 1 week to reassess the dosage. J.M. agrees with this plan.

Case 2. C.P. is currently not taking any other medications and does not have any comorbidities. C.P. has never tried any antidepressant medications in the past. C.P. shares that she is most concerned about weight gain and loss of libido. She is employed as a dental hygienist and does not like dry mouth, but she is able to tolerate it. You believe C.P. would benefit from an antidepressant, but C.P. is worried about starting medications. You review the Antidepressant Decision Support Tool with C.P. and she notices that there may be benefit with bupropion to help with libido in women and it is least likely to cause weight gain. C.P. notes that bupropion may cause dry mouth. In discussion with you, she is agreeable to trying bupropion. You write a prescription for 150 mg of extended-release bupropion daily for C.P. and ask to follow up with her in a week.