FLUOXETINE
In the early days of psychopharmacology there was considerable controversy regarding the role of drug therapy in depression. The prevailing attitude was that drug therapy was the easy way out for both the patient and the doctor.
Early on there were implications that drug therapy required less effort and was not as good as the long and rigorous process of psychotherapy. This attitude is becoming, at best, a minority position today. Pharmacotherapy of depression is no longer accepted as second best to psychotherapy, but is an important and effective treatment that can go hand in hand with psychotherapeutic intervention. In the earlier days of antidepressant drug therapy it was commonly felt that milder, so-called neurotic, depression should be treated without medication, and that medication should be reserved for the more severe depressive illnesses such as psychotic depression. Newer research over the past several years strongly supports the value of pharmacologic intervention, not only in psychotic depression and depression associated with manic-depressive illness, but also in some milder forms of depression which may impair the ability of an individual to be productive and to enjoy life. The changing attitude toward the pharmacotherapy of depression is a manifestation of advancement in our knowledge of the etiology and course of depressive illness. Indeed, the recognition of the high incidence of depression, and the considerable potential for a favorable outcome, has yielded a more definitive therapeutic approach for this serious health problem. The DSM-III, published in 1980 and revised in 1987 (DSM-III-R), has changed the diagnostic categorization of depression in a direction that is more consistent with a biological understanding of psychiatric illness.2
Depressive illness, though it may be categorized in a number of ways, most likely exists along a continuum, from mild to more severe forms, with varying degrees of functional impairment. There is clearly a tendency of depressive illness to run in families; thus, genetic factors appear to be important. Extensive research suggests that the clinical manifestations of depression are related to changes in neurotransmitter function in the brain.5,6 Reserpine, which depletes brain serotonin and norepinephrine, can induce severe depression and even suicidal behavior.2 Methyldopa, a widely used antihypertensive which impairs brain neurotransmitter function, can likewise induce depression.10
Antidepressants are highly effective in alleviating the symptoms of depressive illness and melancholia, including sadness and hopelessness as well as anorexia and insomnia. These drugs may alleviate the feeling of worthlessness and guilt, and improve the patient s ability to engage in formerly pleasurable activities including work and leisure pursuits. As the depressive symptoms subside, patients generally experience an improvement in their energy level, a decrease in fatigue and psychomotor symptoms, and the disappearance of suicidal thoughts.8 The psychiatric literature over the past 25 years has repeatedly documented the high degree of efficacy of tricyclic and heterocyclic antidepressant drugs. Unfortunately, most antidepressants have one serious deficiency, specifically, an extremely long lag time before the appearance of a satisfactory antidepressant response. Most patients require a 2- to 3-week course of treatment before the favorable effects of these drugs become manifest. One of the second-generation tricyclic antidepressants, amoxapine, has been demonstrated in numerous studies to have a rapid onset of action, producing some improvement in mood in a sizable number of patients within four days of initiating drug therapy.11,12 As with other psychiatric medications, the antidepressants produce several unwanted effects, most notably anticholinergic actions and drowsiness. Since these side effects are most prominent early in the course of treatment, many patients discontinue their antidepressant long before it has had time to produce its therapeutic action and alleviate depressive symptoms.8 Since amoxapine may produce significant antidepressant effect within the first few days of treatment, and since its side effects are relatively mild in comparison to many other antidepressants, the clinician may easily be able to convince his patient to tolerate a few days of discomfort while awaiting a therapeutic response.11 Some of the more commonly seen adverse effects of tricyclic and heterocyclic antidepressants are shown in Table 5-3.