Achieving the best outcome in treatment of depression

Journal of Family Practice, March, 2003 by John E. Sutherland, Steven J. Sutherland, James D. Hoehns

A recent randomized, prospective comparison of the SSRIs paroxetine, fluoxetine, and sertraline showed similar effectiveness and tolerability (SOR: A). (31) This suggests that efforts to individualize therapy based on comorbidities or likely side effects may not be as useful when choosing from among analogous SSRIs.

Nevertheless, choosing a drug that is effective, convenient, and well tolerated will improve the likelihood of achieving and maintaining a full remission. The data on adverse effects of antidepressants are widely available and well understood. Also consider cost (Table).

Preferences based on characteristics. For a patient whose depression is not complicated by other clinical conditions, the initial choice of antidepressant would usually be an SSRI. But nefazodone, mirtazapine, bupropion, or low-dose venlafaxine may be equally appropriate.

For a patient whose depression has other specific components, use your knowledge of drugs' common side effects to fit the patient's clinical profile.

* If there is generalized anxiety, agitation, and insomnia, both nefazodone (8) and mirtazapine (32) are excellent choices. Trazodone at low doses is often used as a sedative with nonsedating antidepressants. (8)

* If weight gain is desired, mirtazapine is indicated. (32)

* If tobacco cessation is a secondary goal, bupropion is preferred. (31)

* Those suffering from hypersomnia, retarded depression, cognitive slowing, and pseudo-dementia would benefit from bupropion or venlafaxine. (9)

* For more severely depressed patients, venlafaxine may be advantageous due to its dual serotonergic and noradrenergic activity at moderate to high doses. (34,35,36) Mirtazapine and TCAs are also useful in severe depression, as well as for coexisting chronic pain syndromes. (8) For refractory or atypical depression in motivated and compliant patients, MAOIs my be useful. (8)

When to avoid specific drugs.

* Patients with hypersomnia and motor retardation should avoid nefazodone and mirtazapine. (8,32)

* With obesity, mirtazapine and TCAs are least preferred. (8,32)

* If sexual dysfunction preceded depression, avoid giving SSRIs and venlafaxine. (3)

* Those experiencing agitation and insomnia should avoid bupropion and venlafaxine. (3)

* Seizure disorder is a contraindication to bupropion. (3)

* Hypertension is a relative contraindication to venlafaxine. (3)

* Liver disease is a contraindication to nefazodone. (37)

* Preexisting heart disease and increased suicide risk are both relative contraindications to TCAs. (8)

Helping nonresponders

Patients whose symptoms do not improve with therapy could be switched to a different monotherapy or to multiple drugs. Drug choices for treatment-refractory and nonresponding patients have evolved more by anecdote than by systematic study. (9)

Switch drugs. The benefit of switching patients to another category of antidepressant was recently demonstrated in a study where nearly half of patients who did not respond to an initial antidepressant, whether SSRI or TCA, responded when switched to the alternate agent (SOR: A). (38) It is also beneficial to switch medications within a category (SOR: B). (27,39,40)