Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline.

BACKGROUND: Several different classes of antidepressants have been associated with sexual adverse effects. This double-blind, randomized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment. Depressive symptoms were also monitored. METHOD: One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline (100 mg/day) were screened for entry. Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase. Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were randomly assigned to receive double-blind treatment with either nefazodone (400 mg/day) or sertraline (100 mg/day) for 8 weeks. RESULTS: Nearly 3 times more sertraline-treated patients (76%; 25/33) experienced reemergence of sexual dysfunction (ejaculatory and/or orgasmic difficulty) than did nefazodone-treated patients (26%; 10/39) (p < .001). In addition, patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline. Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms. Both drugs were well tolerated, and the overall incidence of adverse reactions was similar for both treatment groups; however, 9 sertraline-treated patients (26%) discontinued because of adverse events compared with 5 nefazodone-treated patients (12%). Of the patients discontinuing therapy for adverse events, 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event, whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction. CONCLUSION: In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline, nefazodone treatment resulted in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity.

Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression.

Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.

Growth hormone response to edrophonium in Alzheimer's disease.

Neuropathologic data from patients with Alzheimer's disease indicate the presence of neurofibrillary tangles in hypothalamic regions associated with regulation of pituitary hormone release. The authors explored the hypothesis that cholinergic projections to hypothalamic nuclei controlling pituitary growth hormone (GH) release degenerate in Alzheimer's disease. Integrity of cholinergic regulation was tested by assaying the GH response to a presynaptic cholinergic challenge. After administration of the choline esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients. The magnitude of GH blunting was correlated with cognitive and functional deficits. Possible implications of these data for enhanced accuracy in the diagnosis of dementia are discussed.

A controlled double-blind study of high-dose dihydroergotoxine mesylate (Hydergine) in mild dementia.

In a double-blind study of 41 outpatients aged 55 to 80 years with mild memory impairment, the efficacy of dihydroergotoxine mesylate (DEM, Hydergine) at 6 mg per day, administered orally, was tested during a twelve-week period. Specific etiologies for the amnesic syndrome were ruled out by history, physical examination, and laboratory tests. Subjects with a Hamilton Depression Scale rating above 18, ie, possible pseudodementia, were excluded. Physician rating of memory, employing the Inventory of Psychic and Somatic Complaints in the Elderly (IPSC-E), indicated statistically significant improvement of memory function in DEM treated subjects (N = 22) v those on placebo (N = 19), (F = 3.34; df = 1,39; P less than .04). In contrast, structured testing of recent memory using digit symbol substitution and Zahlenverbindungs test (ZVT) showed improvement in both groups (P less than .001) with no significant intergroup differences (P less than .10). Out results indicate that in cases of mild, though subjectively distressing impairment, DEM at higher dosages may help to enhance short-term memory function.

Alcoholism in the elderly.

Alcohol abuse and dependence can be both cause and result of many problems of physical and mental health in old age. In order to develop a comprehensive understanding of the complex and mutually dependent relationships between aging and alcoholism, biologic as well as psychosocial factors must be taken into consideration. Sleep physiology, sexuality, and sensory function have received considerable attention in respect to the changes occurring with increasing age. These areas of functioning seem to be particularly vulnerable when the impact of chronic alcohol abuse is added to the effects of normal aging. The aging brain is another sensitive target for the influence of alcohol, and alcoholism has the potential to significantly aggravate cognitive deterioration. In susceptible individuals, the psychosocial stresses of growing old may erode self-esteem and precipitate depressive disorders. Thus, certain aspects of aging may become pathogenic factors in the development of alcoholism. Our current knowledge in this respect, however, is rather hypothetical and needs validation. Further systematic research is required. The momentum to generate interest in the science of aging, and thus stimulate research into age-related problems, may be provided by demographic developments. The number of Americans aged 65 and older is projected to increase markedly over the next four decades. A substantial part of this growing segment of our population suffers from alcohol dependency. The percentage of alcoholics is particularly high among the elderly in institutionalized care settings. An investment in efforts to better understand the interaction between aging and alcohol, and to develop more effective primary and secondary prevention concepts, could prove most rewarding.

Alcoholism in the geriatric population.

Alcohol abuse by elderly persons may be overlooked by clinicians because the effects of alcoholism on intellectual processes may be attributed to advancing age. In older patients, in whom liver and other organ functions may be reduced, even modest social drinking will impair cognitive abilities. Alcoholism is especially detrimental to older persons because 1) their blood levels of ethanol are higher than those in younger persons, and brain neurons may be more sensitive to the drug; 2) ethanol can disturb their sleep and sexual performance; 3) their cognitive functions may be significantly impaired by ethanol; and 4) for elderly patients, who commonly take a variety of drugs, ethanol and drug interactions are particularly hazardous.

How to minimize side effects of psychotropic drugs.

Aging has a direct effect on drug absorption, distribution, and elimination. With aging, there is an alteration in the neurotransmitters whereby dopaminergic and catecholaminergic systems are relatively depleted of monoamines while acetylcholine is largely unaffected. Pharmacotherapy in the elderly requires an understanding of the physiologic effects of medications. Dosage generally should be lower for the elderly patient on the basis of a milligram per kilogram of body weight, but determining the appropriate dosage required more than allowing for "smaller body mass" or "less body water." Because of lengthened half-life and slowed distribution of medications, it is necessary to start with very low dosages and observe the patient for relatively longer periods of time before giving another dose, increasing the medication, or adding another drug.