Pharmacotherapy

Antidepressant medication has been surprisingly inefficacious for adolescents. In contrast to open studies, placebo-controlled, double-blinded research protocols have failed to demonstrate any benefit of medication over placebo for adolescent depression. Up to 60% of adolescents recover while receiving placebo; up to 70% recover using medication. This finding applies to traditional tricyclic antidepressants, such as imipramine, desipramine, and nortriptyline, and also to serotonin reuptake inhibitors, such as fluoxetine. However, numbers in studies of the more recent medications have been limited.

When is medication indicated? Medication should be considered early in treatment for certain situations:

• psychotic episodes,

• vegetative symptoms,

• severe functional impairment,

• bipolar disorder,

• panic disorder,

• obsessive compulsive disorder, and

• strong family history of depression.

Psychosis and bipolar disorder usually require psychopharmacologic intervention in the form of antipsychotics, benzodiazepines, and mood-stabilizing agents, such as lithium and carbamazepine. The approach is similar to that for adults and is reviewed elsewhere. Medication should be considered seriously when there are comorbid conditions for which antidepressant medications have clearly been demonstrated effective, even for adolescents. These include obsessive compulsive disorder, panic disorder, bulimia, and attention deficit disorder.

Despite the lack of demonstrated efficacy of antidepressant therapy for adolescents, some leading researchers point out that, once placebo responded have been eliminated, a group of patients who appear to respond well to medication remains. Therefore, a trial of medication is justified when a serious major depressive episode fails to respond to nonpharmacologic interventions. Many of these patients have prominent neurovegetative symptoms including severe sleep disturbance, weight change, and marked functional impairment. This approach has produced excellent results in specialty mood disorder clinics, which tend to see more severe cases that have not responded to other treatments.

If the clinical situation indicates medication, which medication is appropriate? Table 3 oudines suggested medications. Factors to consider are the safety profile, side effects, effectiveness of the medication for depression and comorbid conditions, cost, and likelihood of compliance with treatment.

Tricyclic antidepressants.Most of the earlier controlled studies found limited evidence of efficacy for this class of antidepressant, especially imipramine, desipramine, and recently nortriptyline. Because tricyclics are lethal in overdose, they cannot be used if there is a risk of suicidal behaviour, despite their low cost and long history of use. Limiting the amount of medication or placing it in the care of a family member are possible solutions if tricyclics are otherwise strongly indicated. Side effects, such as anticholinergic effects, sedation, and postural hypotension, are common and limit compliance. However, for certain young people, especially those with comorbid obsessive compulsive disorder, attention deficit disorder, or panic disorder, tricyclics are the drugs of choice. Also, controlled studies have shown desipramine helpful for attention deficit disorder and bulimia, and clomipramine is clearly effective for obsessive compulsive disorder.

Serotonin reuptake inhibitors. Because overdoses are not lethal, side effects are minimal, and they have an activating effect on anergic adolescent depression, serotonin reuptake inhibitors are the practical drugs of choice. Comorbid obsessive compulsive disorder, bulimia, and some panic disorder cases will also respond. Preliminary observations on the efficacy of fluoxetine for attention deficit disorder and impulse control disorders suggest that it might be more widely used if supported by future research. Anorgasmia is one upsetting side effect for some patients.

Other pharmacologic agents. Special situations call for other drug classes. Monoamine oxidase inhibitors are effective for the atypical depression, panic disorder, and social phobia often present in adolescent depression. Dietary restrictions, postural hypotension, and sexual dysfunction might limit compliance, and the risk of serious hypertensive crisis is worrying. The introduction of moclobemide, a reversible monoamine oxidase inhibitor that has no dietary restrictions, that is helpful for anxious depression, and that might also be useful for atypical depression, could solve these problems. Overdoses of moclobemide have not proved fatal to date.

Finally, using lithium as augmentation, or for recurrent depression, can be considered for adolescents as for adults, although specific effectiveness for adolescents has not been demonstrated.

Conclusion

The social, psychological, and developmental costs of adolescent depression are well documented. In most cases comprehensive psychosocial intervention is more effective treatment than pharmacotherapy. Because of the risk of recurrence and the presence of identifiable, persistent risk factors, emphasis during both evaluation and treatment must be on assisting the young person to develop more effective coping skills and a more positive cognitive and behavioural style. Current studies are examining the effect of psychological and pharmacologic treatments on outcome.

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