Valproic acid for nonaffective aggression in the mentally retarded.
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Biomedical subjects
Publications and source records attributed to J A Mattes.
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Vasopressin may be involved in normal memory functions and may alleviate certain memory impairments. In this study, the usefulness of vasopressin to relieve electroconvulsive therapy (ECT)-induced memory impairment was evaluated using a placebo-controlled, random assignment, double-blind design. Patients were 33 depressives receiving bilateral ECT. Vasopressin, in a nasal spray, was administered q.i.d. from the first through the fifth ECT. Extensive memory testing evaluated both retrograde and anterograde amnesia; ratings of depression and patient ratings of subjective memory complaints were also obtained. Results did not show statistically significant evidence of benefit from vasopressin, though a number of comparisons were in the predicted direction. The role of vasopressin in reducing memory impairment of various types remains to be elucidated.
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Eighty patients (randomly assigned in 51 cases) with diverse diagnoses, were prescribed propranolol or carbamazepine for temper outbursts. Results suggested that both medications were beneficial. The diagnosis of attention deficit disorder predicted preferential response to propranolol, and a diagnosis of intermittent explosive disorder predicted preferential response to carbamazepine. Results, however, were not entirely consistent and require confirmation.
Clozapine is a novel antipsychotic agent that selectively blocks mesolimbic--rather than nigrostriatal--dopamine receptors, causes fewer extrapyramidal symptoms than do other neuroleptics, and has superior antipsychotic efficacy in some patients. However, clozapine also causes agranulocytosis more frequently than do other neuroleptics. The evidence documenting the superior benefits obtained with clozapine has primarily involved short-term (4-6 weeks) trials, and the systematic evaluation of long-term clozapine use has been limited. In this study, 14 patients with refractory chronic schizophrenia were treated openly with clozapine up to 2 years; 8 did substantially better when given clozapine than they had when given other neuroleptics. That finding suggests that clozapine may provide a useful addition to the therapeutic armamentarium for the long-term treatment of schizophrenia, despite the increased risks and the need for frequent blood tests.
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The effect of stimulants on growth has been controversial. Among hyperactive children receiving long-term methylphenidate hydrochloride treatment, we examined the effects of methylphenidate withdrawal on the growth of hyperactive children randomly assigned to be taken off, or remain on, the medication regimen over two consecutive summers. After one summer, no group difference in height was found, but weight was higher in the group that had been taken off methylphenidate therapy. In contrast, two summers of being off methylphenidate treatment had a significant positive effect on height but not on weight. The results document a linkage between exposure to methylphenidate and reduction in growth velocity. However, they do not address whether the medication has long-term effects on height.
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To evaluate the heritability of a personality trait, "having temper outbursts," and of associated diagnoses, we obtained histories of first degree relatives on two groups: (1) patients with temper outbursts (N = 33), and (2) diverse psychiatric patients without temper outbursts (N = 12). Family interviews were conducted blind to patient (temper or not) status, using a modified version of the Family History RDC. Though Ns are relatively small, and results therefore require confirmation, the data indicate familial transmission of temper problems; an average of 18.2% of Group 1 relatives had temper problems, compared to 4.3% for Group 2. The trait of having temper outbursts was more strongly transmitted than were specific diagnoses (e.g. Intermittent Explosive Disorder, Antisocial Personality Disorder or Residual Attention Deficit Disorder) associated with temper outbursts. Patients with neurological conditions apparently related to their temper outbursts were less likely to have positive family histories.
An open pilot trial of combined trazodone and tryptophan for 11 patients with Obsessive-Compulsive Disorder was conducted to test the hypothesis that increasing serotonin activity is therapeutic for this condition. Results were not encouraging; several patients tolerated the combination poorly, but even among patients completing 2 weeks' treatment benefit was marginal.
Recent studies suggest that several drugs, specifically carbamazepine, propranolol, and lithium, may alleviate rage outbursts. This literature is reviewed and possible mechanisms of action are discussed.
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Thirteen adults with temper outbursts and residual attention deficit disorder (ADD) were given propranolol to 640 mg/day in an open study. Eleven of the patients improved, with improvement in temper and other symptoms of ADD, indicating a need for controlled studies. This suggests a novel pharmacological approach to residual ADD.
Ceruletide, an analog of cholecystokinin (CCK), has been reported to have neuroleptic-like activity in mice, and, in three open studies, to benefit schizophrenic patients. This study evaluated ceruletide in schizophrenia using a double-blind design. Subjects were 17 chronic schizophrenics with residual symptoms following stabilization with neuroleptics. Patients randomly received two injections, 1 week apart, of either ceruletide (0.6 microgram/kg im) or placebo, while continuing neuroleptics; this regimen was found helpful in earlier studies. Evaluation included ratings of 29 variables related to prognosis in schizophrenia (e.g., age, number of previous hospitalizations), regular BPRSs and SCL-90s, and psychiatrist, patient, and relative ratings of global improvement. Results showed few significant differences between ceruletide and placebo, with exceptions as likely to favor placebo as ceruletide. Among the patients on ceruletide, no predictors of benefit were found. Possible reasons for the negative results are discussed.
Ceruletide, a cholecystokinin analogue, has been reported to interact with dopamine in the CNS and to benefit schizophrenic individuals. The authors, using a double-blind design, a higher total dose, and a larger sample size than previous studies, found no evidence of benefit.