PART 6 in Microsoft Office

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neurotrophic factors is at least consistent with this view and with the hypothesis that one component of recovery from depression is in some way associated with restoration of normal neuronal architecture in regions of the hippocampus and the hypothalamus (Chen) Although highly speculative, perhaps some of these changes explain the delay in improvement after the administration of antidepression drugs At the present time, it must also be conceded that there is no reliable biologic test for depression One must resort to clinical analysis (ie, the interpretation of symptoms and signs) not only for diagnosis but also for the differentiation of special types of depressive reactions Psychosocial Theories 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 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 or personality makeup Perhaps the genetically transmitted factor is a heightened vulnerability to the effects of psychosocial stress Epidemiologic data favoring one or another of these speculations are lacking One is tempted to conclude that many depressions attributed to psychosocial stress are contaminating a group of endogenous depressions Psychiatrists have also failed to nd a consistent correlation between depressive illness and personality type or a particular psychodynamic mechanism In our view, the adoption studies noted tend to diminish the importance of environmental factors in explaining most major depressions

The use of medications for depression is now so widespread that all physicians should be familiar with them The physician untrained in psychiatry would, however, be unwise to undertake the management of manic-depressive disease or endogenous depression without the advice or assistance of a psychiatrist If the symptoms are primarily neurologic (eg, chronic headache, generalized weakness and fatigability) and if there is a low risk of suicide, it is appropriate for the experienced neurologist or generalist to institute treatment with antidepressant medication If there is any suspicion of suicide, the patient should be hospitalized and, if necessary, involuntarily committed Antidepressant Medication In the management of bipolar and unipolar disease, ve 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), and lithium The pharmacologic properties and modes of action of these drugs have already been considered in Chap 43 (pages 1026 to 1028) Additional points of therapeutic interest are mentioned here It should also be stated that meta-analyses of several large studies on the therapeutic effects of antidepressants have suggested that clinical improvement attributable to the drugs themselves occurs in only about one half of patients; remarkably, an

additional improvement in up to 25 percent has been attributable to a placebo effect or to the natural course of the disease The remainder fail to improve in a timely manner or relapse while on medication Most psychiatrists currently prefer to begin treatment with one of the functional serotonin agonists (SSRIs) uoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and others, or one of a related group, exempli ed by venlafaxine (Effexor) and nefazodone (Serzone) New ones of similar type are appearing yearly These drugs have less sedating and anticholinergic effects than the tricyclic antidepressants discussed later 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, ie, weight gain Patients with anorexia, insomnia, and high levels of anxiety may do better with a more sedating medication, such as amitriptyline In a similar vein, uoxetine would be a reasonable choice for patients in whom lethargy is a prominent complaint Certain side effects such as loss of libido or impotence occur in a proportion of patients and are dif cult to differentiate from the signs of depression The tricyclic antidepressants comprise amitriptyline (Elavil), imipramine (Tofranil), doxepin (Sinequan), clomipramine (Anafranil), and trimipramine (Surmontil), and the closely related drugs desipramine (Norpramin), nortriptyline (Pamelor), and protriptyline (Vivactil) Among this group, most psychiatrists start with imipramine or amitriptyline because of their relative safety In general, all of these drugs are equally effective, although an individual patient may have a better response to one than to another The starting dose for amitriptyptine or imipramine is 25 mg/day, which is then raised by 25 mg every 3 to 4 days as needed up to 150 mg/ day These drugs, taken at bedtime, are also very helpful in alleviating the insomnia that accompanies depression The therapeutic effect of tricyclic medication is generally not evident for 2 to 4 weeks after treatment has been initiated, and it is important that this be explained to the patient and family Common side effects are orthostatic hypotension, dry mouth, constipation, tachycardia, urinary hesitancy or retention (especially in patients with prostatic hypertrophy), tremor, and drowsiness Closed-angle glaucoma may decompensate Caution should be exercised in elderly patients with cardiac disorders of all types For such patients, the serotonin drugs or one of a newer group of nontricyclic antidepressant drugs bupropion (Wellbutrin) and trazodone (Desyrel) may be preferable The latter drugs appear to be as effective as the tricyclic agents in the treatment of depression without the adverse anticholinergic and cardiotoxic effects If one of the aforementioned drugs, given in full doses for 4 to 6 weeks, does not produce the desired effect (or if the patient is intolerant of the given drug), another one from an alternative group, eg, an MAO inhibitor, may be tried In the case of SSRIs, there must be a drug-free interval of 1 to 2 weeks before instituting an MAO inhibitor Some studies suggest that MAO inhibitors are superior in depression with atypical features such as increased appetite Phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate) are in this category, of which the rst is said to be the least likely to produce serious side effects The usual starting dose is 15 mg tid, which is gradually increased as needed to a maximum of 45 mg tid The most serious risk of MAO inhibitors is the occurrence of a hypertensive crisis; therefore, these drugs should be dispensed with caution in patients with hypertension and with cardiovascular or cerebrovascular disease Patients