DEPRESSION

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Depression

Management of Major Depressive Disorder: Pharmacotherapy

Adapted from: Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord 2009;117 (suppl 1):S26-43.

OVERVIEW

The principles behind pharmacotherapy management for major depressive disorder are similar to those for other treatment modalities (see Key Points, following), but patient adherence to treatment is a particular challenge and is given particular attention in these guidelines. Rates of early discontinuation are high, generally because of lack of response, stigma associated with having a psychiatric illness, and side effects. Finding ways to optimize adherence to treatment when prescribing antidepressants is essential and should incorporate education and self-management strategies for patients and collaborative care systems for practitioners.

KEY POINTS

KEY POINTS

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CHOOSING A FIRST-LINE ANTIDEPRESSANT

CHOOSING A FIRST-LINE ANTIDEPRESSANT

The results of an individual assessment, tolerability, patient preference, and cost all must be taken into account when selecting a first-line medication. Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and newer agents have better safety and tolerability profiles than older medications such as tricyclic antidepressants (TCAs) and monoamine oxidase (MAO) inhibitors, which are recommended second-line. Other second-line agents include trazodone and quetiapine.

Table 2.

TABLE 2. SUMMARY INFORMATION FOR ANTIDEPRESSANTS
  • Table 1

Factors influencing the choice of first-line antidepressant

Factors influencing the choice of first-line antidepressant

Side effects

Common side effects depend on the antidepressant chosen, but may include the following:

  • Gastrointestinal (GI) side effects (e.g., nausea, diarrhea).
  • Central nervous system side effects (e.g., headache, insomnia, sedation, nervousness, and tremor).
  • Metabolic side effects (e.g., appetite stimulation, weight gain, disturbances in the lipid milieu, glucose homeostasis).
  • Other adverse events:
    • Alterations in heart rate and blood pressure.
    • Elevation of liver enzymes.
    • Withdrawal symptoms (with abrupt discontinuation, dose reduction or tapering).

Side-effect management may be an option for patients who have achieved a response with a particular antidepressant but continue to be troubled by side effects.

Potential serious adverse effects

Potential serious adverse effects

  • Possible emergent suicidality in children and adolescents (see Table 9).
  • Rarely, serotonin syndrome or neuroleptic malignant syndrome-like events (if SSRIs/SNRIs are co-prescribed with MAO inhibitors or other serotonergic agents).
  • Possible increased risk of upper GI bleeding with SSRIs, especially in combination with NSAIDs.
  • Possible increased risk of osteoporosis and fractures in the elderly with SSRIs.
  • Hyponatremia and agranulocytosis in a small percentage of patients.
  • Increased risk of seizures with TCAs at therapeutic doses.

Drug–drug interactions

Drug–drug interactions

Polypharmacy is common in patients with MDD. Most of the drug interactions with antidepressants involve the cytochrome P450 (CYP) enzyme metabolic pathway or p-glycoprotein, a membrane transporter.

Table 3.

TABLE 3. POTENTIAL FOR DRUG–DRUG INTERACTIONS AMONG FIRSTLINE ANTIDEPRESSANTS
  • Table 1

Sexual dysfunction

Sexual dysfunction

Many antidepressants also disturb sexual function. Dose reduction, if possible, is sometimes beneficial. Many patients will require a switch to another antidepressant with a lower propensity to cause sexual dysfunction, including agomelatine, bupropion, mirtazapine, moclobemide, and selegiline transdermal.

Other factors

Other factors

Other clinical factors that should influence antidepressant selection are shown in Table 4.

Table 4.

TABLE 4. CLINICAL FACTORS THAT INFLUENCE ANTIDEPRESSANT SELECTION
  • Table 1

Summary

Summary

Table 5.

TABLE 5. SUMMARY RECOMMENDATIONS FOR PHARMACOTHERAPY
  • Table 1

Managing non-response or incomplete response

Managing non-response or incomplete response

Figure 1.

FIGURE 1. ALGORITHM FOR MANAGING LIMITED IMPROVEMENT WITH A FIRST-LINE ANTIDEPRESSANT
  • Table 1

Table 6.

TABLE 6. RECOMMENDATIONS FOR NON-RESPONSE AND INCOMPLETE RESPONSE TO AN INITIAL ANTIDEPRESSANT
  • Table 1

Table 7.

TABLE 7. RISK FACTORS SUPPORTING LONG-TERM (2 YEARS TO LIFETIME) ANTIDEPRESSANT MAINTENANCE
  • Table 1

Special populations

Special populations

Below are recommendations for pharmacotherapy of MDD in pregnant/nursing women, and in youth.

Table 8.

TABLE 8. RECOMMENDATIONS FOR PHARMACOTHERAPY OF MDD IN PREGNANCY AND POSTPARTUM
  • Table 1

Table 9.

TABLE 9. RECOMMENDATIONS FOR PHARMACOTHERAPY IN YOUTH WITH MDD
  • Table 1

CONCLUSION

CONCLUSION

All second-generation antidepressants have demonstrated efficacy and tolerability, and most can be considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants should be used as second- or third-line treatments. Switching therapies or add-on therapies may be considered, if patients experience inadequate or incomplete response.

Full guidelines

Full guidelines

The preceding material represents a summary of the CANMAT guidelines for the management of major depressive disorder. Clinicians are encouraged to consult the complete document (see Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009;117(suppl 1):S26-43).

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