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 nefazodone8 and mirtazapine32 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 pseudodementia 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
TABLE
Comparative dosages and costs of antidepressant drugs
| Agents | Initial target dose | Maximum effective dose | Monthly cost of initial target dose* |
|---|---|---|---|
| Selective serotonin reuptake inhibitors | |||
| Citalopram (Celexa) | 20 mg qd | 60 mg qd | $61.58 |
| Escitalopram (Lexapro) | 10 mg qd | 20 mg qd | $65.28 |
| Fluoxetine (Prozac) | 20 mg qd | 80 mg qd | $81.78 |
| Fluoxetine (generic) | 20 mg qd | 80 mg qd | $61.80 |
| Fluoxetine (Prozac Weekly) | 90 mg qwk | $71.04 | |
| Fluvoxamine (Luvox) | 50 mg qd | 150 mg bid | $59.70 |
| Paroxetine (Paxil) | 20 mg qd | 60 mg qd | $70.98 |
| Paroxetine (Paxil CR) | 25 mg qd | 75 mg qd | $75.86 |
| Sertraline (Zoloft) | 50 mg qd | 200 mg qd | $65.24 |
| Tricyclic antidepressants | |||
| Amitriptyline (Elavil, Endep, Vanatrip) | 100 mg qhs | 300 mg qhs | $ 7.99 |
| Desipramine (Norpramin) | 100 mg qhs | 200 mg qhs | $18.54 |
| Doxepin (Adapin, Sinequan) | 100 mg qhs | 300 mg qhs | $8.12 |
| Imipramine (Tofranil) | 100 mg qhs | 300 mg qhs | $31.96 |
| Nortriptyline (Aventil, Pamelor) | 75 mg qhs | 150 mg qhs | $ 8.71 |
| Others | |||
| Bupropion (Wellbutrin) | 100 mg tid | 150 mg tid | $92.33 |
| Bupropion (generic) | 100 mg tid | 150 mg tid | $64.62 |
| Bupropion (Wellbutrin SR) | 150 mg bid | 200 mg bid | $87.09 |
| Mirtazapine (Remeron) | 30 mg qhs | 45 mg qhs | $80.79 |
| Nefazodone (Serzone) | 100 mg bid | 300 mg bid | $74.94 |
| Trazodone (Desyrel) | 100 mg bid | 300 mg bid | $15.98 |
| Venlafaxine (Effexor) | 37.5 mg bid | 150 mg tid | $74.39 |
| Venlafaxine (Effexor XL) | 75 mg qd | 225 mg qd | $66.25 |
| Lithium (Eskalith, Lithobid, Lithonate, Lithotabs) | 300 mg bid | 600 mg bid | $13.70 |
| *Costs from www.drugstore.com, November 2002. | |||
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
Add a drug. Adding a second antidepressant from a category with a different mechanism of action often enhances clinical efficacy. This has been demonstrated in combining an SSRI with a TCA (SOR: B).41 Though response rates are very similar for various antidepressants, complete remission and rates of response in severely depressed patients may be higher in dual-action antidepressants (SOR: A).34,35,36
Add lithium. A great deal of evidence supports the use of lithium augmentation (SOR: A).42,43 This agent should be used more in primary care and not only by psychiatrists. A recent meta-analysis of double-blind, placebo-controlled studies of lithium (given at a dosage of at least 800 mg/d or at a level high enough to achieve a serum drug concentration of 0.5 mEq/L for at least 2 weeks) found a summary pooled odds ratio of response to lithium of 3.31 (95% CI, 1.46–7.53) with a NNT of 3.7.44 Other studies have been less clear on the optimal dose or blood level, so a starting dose of 300 mg twice daily with a serum drug concentration of 0.4 mEq/L has been recommended.
If renal function is normal, the concentration of lithium can be checked 5 days after a patient has received a stable dosage, at least 8 hours fol-lowing the last dose. Lithium may cause thyroid abnormalities; monitoring should include a measurement of thyroid-stimulating hormone, repeated at 6 months and 1 year.
Other augmentation options. Augmentation of antidepressants with buspirone has been proven useful in major depression (SOR: B).45 Thyroid supplementation may also increase the effectiveness of antidepressant therapy using triiodothyronine (T3), at doses not to exceed 50 mcg per day (SOR: B).46,47 Electroconvulsive therapy (ECT) has a high rate of therapeutic success, including speed and safety, but it is not administered as first-line treatment by psychiatrists except in severe cases (SOR: A).48,49 Augmentation with antipsychotic or anticonvulsants is another strategy that shows some benefit for select patients.50