Many experienced psychiatrists have emphasized the importance of psychosocial factors in the genesis of depressive illness. Among patients with primary depressive disorders, life events of a stressful nature were found to have occurred more frequently in the months preceding the onset of depression than in matched control groups. In the study by Thomson and Hendrie, this was equally true of patients with a positive family history of depression and of those without such a history. Nor did patients with endogenous depression differ in this respect from those with reactive depression. Left unanswered is the question of why some individuals are subject to a reactive depression. Are they predisposed by psychologic, personality, or genetically transmitted factors of heightened vulnerability to the effects of psychosocial stress? One is tempted to conclude that many depressions attributed to psychosocial stress are contaminating a group of endogenous depressions. Psychiatrists have also failed to find a consistent correlation between depressive illness and personality type or a particular psychodynamic mechanism. The biopsychosocial theories of mental illness have the most appeal in explaining depression but which elements are operative in any individual are difficult to discern.
The use of medications for depression is now so widespread that all physicians should be familiar with them. It must be acknowledged, however, that the magnitude of the effect on depression of these medications has been dominated by a few clinical trials. Meta-analyses of several large studies on the therapeutic effects of antidepressants suggest that clinical improvement attributable to the drugs themselves occurs in approximately 50 percent of patients; remarkably, an additional improvement in up to 25 percent is attributable to a placebo effect or, more likely, to the natural course of the disease. The remainder fails to improve in a timely manner or relapse while on medication. The incremental value of certain forms of psychotherapies is discussed further on.
Those untrained in psychiatry would be unwise to undertake the management of bipolar disease or a serious endogenous depression without the advice or assistance of a psychiatrist. On the other hand, if the symptoms are primarily neurologic (e.g., chronic headache, generalized weakness, and fatigability) and if there is a low risk of suicide, it may be appropriate for the experienced neurologist to institute treatment with antidepressant medication.
In the management of bipolar and depressive disease, six main categories of drugs are in general use—the tricyclic antidepressants, the “atypical” or nontricyclic group of compounds, the MAO inhibitors, serotonin agonists (reuptake inhibitors), antiepileptic drugs, and lithium. The pharmacologic properties and modes of action of these drugs were considered in the context of their side effects in Chap. 41. Additional points of interest are mentioned here.
Most psychiatrists currently prefer to begin treatment with one of the functional serotonin agonists (SSRIs)—fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and others, or one of a related group (serotonin-norepienphrine reuptake inhibitors), exemplified by venlafaxine (Effexor) and nefazodone (Serzone). New drugs of similar type are appearing yearly. These drugs have less sedating and anticholinergic effects than the tricyclic antidepressants discussed below, and may have a slightly faster onset of effect against depression. Fluoxetine has a tendency to produce insomnia and weight loss, making it particularly useful in the treatment of depressions that are characterized by overeating and hypersomnia. Some female patients have experienced an opposite effect, that is, weight gain. Patients with anorexia, insomnia, and high levels of anxiety may do better with a more sedating medication, such as amitriptyline. Fluoxetine would be a reasonable choice for patients in whom lethargy is a prominent complaint.