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Ratings on the Sexual Symptom Checklist, plasma oxytocin, serum paroxetine and clomipramine levels, and Yale-Brown Obsessive-Compulsive Scale scores.
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5-hydroxytryptamine (5-HT) (3 X 10(-9) to 10(-6) M) produced a concentration-related inhibition of potassium-evoked tritium release from slices of rat hypothalamus preloaded with [3H]-5-HT. The response to 5-HT was unaffected by the presence of yohimbine (10(-6) M), pimozide (10(-7) M), domperidone (10(-7) M) or tetrodotoxin (10(-7) M), indicating that the response was not mediated via alpha 1- or alpha 2-adrenoceptors or dopamine receptors and that the receptors that were involved were located directly on the 5-HT nerve terminal. The 5-HT antagonist metergoline (10(-8) to 3 X 10(-7) M) produced a parallel rightward shift in the concentration-effect curve to 5-HT with no reduction in the size of the maximum response. The pA10 value for metergoline was 6.82 and the slope of the Arunlakshana-Schild plot was not significantly different from 1.0 indicating that it was a competitive antagonist. Methiothepin produced a similar effect to metergoline whilst cyproheptadine and methysergide were less potent as antagonists of 5-HT and were not competitive. Cinanserin was inactive. Thus we have characterized the 5-HT autoreceptor in the rat hypothalamus using a classical pharmacological approach and found that it has more in common with the autoreceptor which we have previously identified in the raphe nuclei of the rat than it has with the 5-HT receptor located on dopamine neuroterminals in the striatum.
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p,p'-DDT (100 to 600 mg per kilogram orally) produced spontaneous and stimulus-sensitive myoclonus in mice and rats. Drugs that enhance brain serotonergic activity reduced p,p'-DDT-induced myoclonus, and serotonin antagonists invariably aggravated this syndrome. p,p'-DDT-treated rats had increased concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in seven regional areas, but serotonin was increased only in the midbrain and cerebellum. We postulate that p,p'-DDT-induced myoclonus may be causally related to blockage of serotonin receptors or inhibition of serotonin release into the synapse, resulting in functional deficiency of this neurotransmiter at the receptor site.
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Trichotillomania is a psychiatric condition characterized by compulsive hair pulling. Three interventions have been studied in the treatment of trichotillomania: habit-reversal therapy (HRT) and pharmacotherapy with either selective-serotonin reuptake inhibitors (SSRI) or clomipramine. This systematic review compared the efficacy of these interventions in blinded, randomized clinical trials. The electronic databases of Medline, Premedline, PsychINFO, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant trials using the search terms "trichotillomania" or "hair pulling." Trials were eligible for inclusion if they compared habit-reversal therapy, SSRI pharmacotherapy, or clomipramine pharmacotherapy to each other or placebo and employed randomization and blinded assessment of outcome. Our primary outcome measure was mean change in trichotillomania severity. The summary statistic was standardized mean difference. Seven studies were eligible for inclusion in this review. Overall, meta-analysis demonstrated that habit-reversal therapy (effect size [ES] = -1.14, 95% confidence interval [CI] = -1.89, -.38) was superior to pharmacotherapy with clomipramine (ES = -.68, 95% CI = -1.28, -.07) or SSRI (ES = .02, 95% CI = -.32, .35). Clomipramine was more efficacious than placebo, while there was no evidence to demonstrate that SSRI are more efficacious than placebo in the treatment of trichotillomania. Future studies on trichotillomania should seek to determine if HRT can demonstrate efficacy against more rigorous control conditions that account for non-specific effects of therapy and determine if HRT can be an effective intervention for trichotillomania beyond the few sites where it is currently practiced in research studies. Future therapy and pharmacotherapy studies in trichotillomania should employ larger sample sizes and intention-to-treat analysis and seek to validate clinical rating scales of trichotillomania severity.
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Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicity.
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We report a patient who experienced delusional symptoms during gradual discontinuation of low-dose venlafaxine and required antipsychotic treatment.
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Basal prolactin concentrations were measured before treatment in 18 children and adolescents with obsessive-compulsive disorder as well as in 15 of these patients after 4 and 8 weeks of clomipramine treatment. Basal prolactin levels were influenced by a history of chronic tic disorder and by the duration and severity of obsessive-compulsive symptoms. Clomipramine administration significantly increased basal prolactin levels. A slight decline in prolactin levels during the last 4 weeks of clomipramine treatment was positively correlated with a favorable treatment response and negatively correlated with duration of illness. If the changes in prolactin levels observed during clomipramine treatment are due primarily to changes in serotonergic neurotransmission, these data suggest that clomipramine treatment of obsessive-compulsive disorder produces an adaptive decrease in the responsiveness of serotonergic receptors.
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The author reviews case reports, case series, and animal studies derived from a MEDLINE search for English language articles on the topics of the effects of psychiatric disorders on sexual functioning, the biology of sex, rates of sexual dysfunction associated with each medication class, and treatment approaches when these side effects occur.
In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters.
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Body dysmorphic disorder, preoccupation with an imagined defect in appearance, is included in DSM-III-R but has received little empirical study. The authors investigated the demographics, phenomenology, course, associated psychopathology, family history, and response to treatment in a series of 30 patients with the disorder.
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Neonatal treatment with clomipramine (CLI) has been shown to have reliable behavioral and biological changes that mimic major symptomatic and biochemical changes found in depression. This paper further explores a common feature of depression, the comorbidity of seizure activity and depressive behaviors in this mode.