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The present series of studies of CSF monoamine metabolites support the hypothesis of a role for serotonin in depressive illness, insofar that depressed patients have slightly lower CSF 5-HIAA concentrations than normal controls. Apparently a normal association between CSF 5-HIAA and platelet MAO activity is disrupted in depression. The importance of serotonin does not, however, appear to be confined to depressive illness. There is a strong association between a low CSF 5-HIAA and a tendency to suicidal behaviour, also outside the setting of depression. The nature of this relationship is unclear, but it is suggested that certain personality features may form a mediating link. A connection between a low serotonin turnover and a weakened control of aggressive or hostile impulses is one possibility.
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There was no significant difference between two groups of patients in response to tricyclic antidepressants and selective serotonin reuptake inhibitors. Selective Serotonin Reuptake Inhibitors show less adverse effects compared to tricyclics, so they appeared to be better tolerated.
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A "high-performance" liquid-chromatographic method is presented for monitoring the therapeutic concentrations, in plasma, of eight tri- and tetracyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine, maprotiline, and protriptyline) and their major active metabolites. One of two internal standards is added to 0.5 mL of drug-containing plasma, the pH is adjusted to about 9.5 with borate buffer, and the sample is extracted with isoamyl alcohol in hexane. The extracts are chromatographed on a column of silica and absorbance of the effluent is measured at either 214 or 254 nm. Chromatographic response is linearly related to concentration for all components over a 5-500 ng range. Analytical recovery of the drugs and metabolites from plasma is approximately 75 to 85% at low and high concentrations. Within-run and day-to-day precision (CV) is less than 5% for both high and low concentrations of most of these drugs and metabolites. Parallel analysis of clinical samples by gas chromatography indicates that results by the two techniques are comparable. We report some results of therapeutic monitoring of clinical samples.
Headache was classified, in conformity to the classification of headache as specified by the Ad Hoc Committee, into migraine, contraction and combined types and others. Tricyclic antidepressant clomipramine having pharmacological properties, which are said to relatively and uniquely inhibit the reuptake of serotonin in the synapses, was administered for headaches and the clinical effects on headaches were examined. Headaches assumed to be attributable to depression were excluded by means of quationing and Zung's self-rating depression scale. Furthermore, the MMPI, MPI and MAS mentality tests were also employed to clarify the characters and traits of these patients with headache. Also, the biochemical mechanism playing a part in the occurrence of headache was conjectured from the pharmacological action pattern of the antidepressant.
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1 The change in forebrain 5-hydroxyindoleacetic acid (5-HIAA) concentration induced by raphe stimulation has been studied in rats treated with Li+ or 0.9% w/v NaCl solution (saline) for 10 days. 2 Raphe stimulation increased the forebrain concentration of 5-HIAA in both groups of animals. Chlorimipramine abolished this effect in the control group, but not in the Li+ group. 3 The inhibition of 5-hydroxytryptamine (5-HT) uptake by chlorimipramine was not affected by pretreatment with Li+ or by the addition of Li+ to synaptosomal suspensions in vitro. 4 It is suggested that the production of 5-HIAA following raphe stimulation in Li+-treated animals is derived from the metabolism of 5-HT which remains within the intracellular environment. The consequence of this in relation to transmitter release is discussed.
The efficacy and the safety of moclobemide (400-600 mg/day), a reversible and selective inhibitor of monoamine oxidase-A (RIMA) and of clomipramine (100-150 mg/day) were compared respectively in 98 and 93 nonmelancholic, nonpsychotic out-patients with a DSM-III major depressive episode over 6 weeks and up to 3 months, in a multi-center double-blind trial. No statistically significant difference between the treatments was found on the number of responders, at 6 weeks and 3 months, to the Hamilton Depression Rating Scale (HDRS), which was the main criterion for efficacy. The sample size was sufficient to detect a difference of approximatively 20% in response rates. Reduction of the total scores on HDRS and Covi anxiety scale was comparable for both treatments, but the reduction on the Retardation Depressive Scale (RDS) was significantly higher with moclobemide at the 1- and 2-week assessments. According to the RDS as well as the global impression of both patient and physician, a somewhat earlier onset of antidepressant action was evident in the moclobemide group. Tolerance was significantly better in the moclobemide group, mainly due to a lower frequency of weight gain, sedation and anticholinergic effects.
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Myoclonic movements have been observed in depressed patients receiving therapeutic doses of clomipramine. Such movements, which appear in states of deep muscular relaxation such as sleep, do not appear to have any repercussion in the outcome of the depression and are reversible following withdrawal of the drug. In this study the plasma levels of clomipramine and desmethylclomipramine were determined and their possible relationship with myoclonus studied. No statistically significant relationships were found.
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Amitriptyline was the most common first line drug of choice among both psychiatrists and general practitioners. The patterns of choice of antidepressants in the two areas accorded with prescribing patterns in two independent prescription surveys. Amitriptyline was chosen even more frequently for severe depression and depression with severe insomnia. Clomipramine was chosen comparatively more often for depression with severe anxiety. Low toxicity compounds (mainly lofepramine, mianserin, and moclobemide) were more often the drug of choice in depression associated with overt risk of suicide. Amitriptyline and clomipramine were used extensively for disorders other than depression (40% and 54% of prescriptions, compared with 13-19% for some other major antidepressants).
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Obsessive-compulsive disorder is a fascinating and troubling clinical problem that is now believed to be relatively common. New approaches to research are beginning to unlock its secrets and explore its biological underpinnings. Drugs such as fluoxetine hydrochloride (Prozac) and clomipramine hydrochloride (Anafranil) now offer hope for improvement in the lives of affected persons.
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Saudi patients with narcolepsy have the same clinical presentation as reported in the Western literature. Narcoleptics with cataplexy had disturbed quality compared to narcoleptics without cataplexy. A long time was reported between symptoms onset and diagnosis, which may reflect the under-recognition of the problem among physicians.
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Treatment with olanzapine, 5HT-2 and D1/ D2 antagonist, significantly improved the clinical picture as Boyd et al. have described in their systematic review.
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Premature ejaculation (PE) is recognized to be the most common male sexual disorder. PE provides difficulties for professionals who treat this condition because there is neither a universally accepted definition nor a medication approved by the Food and Drug Administration (FDA). Despite these shortcomings, physicians continue to diagnose their patients with PE according to major guidelines and treat them with either behavioral therapies or off-label medications. This review focuses on current and emerging treatment options and medications for PE. Advantages and limitations of each treatment option are discussed in the light of current published peer-reviewed literature.
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Obsessive-compulsive disorder (OCD) is a chronic debilitating condition that requires long-term treatment. The selective serotonin reuptake inhibitors (SSRIs) appear to be associated with similar levels of efficacy to clomipramine in short-term treatment, but to have significant tolerability advantages. The results of the long-term controlled studies on clomipramine, fluvoxamine, fluoxetine and sertraline are reviewed. They demonstrate a significantly better outcome for anti-obsessional drugs than placebo. The absence of adequate long-term controlled studies on pharmacotherapy strengthen the grounds for recommending pharmacotherapy as the optimal approach for long-term treatment of OCD. The SSRIs would appear to be the treatment of choice in OCD in view of their tolerability and safety advantages compared with clomipramine.
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A case is described of a patient with a history of several years of diazepam abuse (in the last 24 months at dosages of 120 mg/d). A tapering schedule was carried out during a 12-day stay in the hospital in which the diazepam dosage was reduced by a fixed quantity every day, corresponding to about ten percent of the initial dosage. Five days after discharge from the hospital the patient experienced panic attacks, for the first time, which continued until 13 days after discharge. By the 40th day, the patient was experiencing a major depressive episode, which improved after administration of clomipramine therapy. We suggest that a relatively quick withdrawal schedule (ten percent per day) is probably inadequate in preventing withdrawal reactions to long-acting benzodiazepines taken in high doses for an extended period of time.
Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated.
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1. Research on the evolution of experimental pain perception and on the achievement of analgesia with ageing has led so far to contradictory results. 2. This study investigated in the rat the impact of ageing on the antinociceptive effect of reference analgesics, acetaminophen (50, 100, 200, 400 mg kg(-1) po), aspirin (50, 100, 200, 400 mg kg(-1) sc), clomipramine (5, 10, 20, 40 mg kg(-1) sc) and morphine (1.25, 2.5, 5, 10 mg kg(-1) sc). 3. Lou/c rats were chosen because they provide a model of healthy ageing and they do not develop obesity with age. Three groups of 40 rats each (mature (4 months), middle-aged (18 months) and old (26 months)), were treated with each drug at 14 days interval. Two tests were used: a thermal test (tail immersion in 48 degrees C water and measurement of reaction latency) and a mechanical test (paw pressure and measurement of struggle threshold). 4. Results confirm the increased mechanical sensitivity to pain and no change in thermal sensitivity for old rats compared to mature and middle-aged animals. They show a marked decrease in the effect of morphine with age and no age-related effect for acetaminophen, aspirin or clomipramine. Plasma levels of morphine and metabolites are not different in the three age groups. 5. It is likely that the influence of age on morphine analgesia is linked mainly to pharmacodynamic rather than pharmacokinetic changes.
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Mice differentiated by their running wheel activity into low and high active animals were chronically treated with the nootropics meclophenoxate, piracetam, vinpocetine, methylglucaminorotate, and the antidepressants lithium, desipramine, amitriptyline, and clomipramine. The influence of chronic drug treatment on running-wheel activity and open field locomotor behaviour was analyzed. Whereas with antidepressants rather sedative effects were observed in both activity types, the effects of nootropics were different in high and low active mice. Running-wheel scores increased in low active mice but decreased in high-active animals with an improvement in efficiency of locomotor behaviour in the open field of these mice after chronic nootropic treatment. In general, the effects of antidepressants seemed to be more uniform than those of the nootropics used.
Forty-six outpatients suffering from moderate to severe panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to a 10-week treatment protocol of regular aerobic exercise (running), clomipramine (112.5 mg/day), or placebo pills.
The effects of the tricyclic antidepressant clomipramine were studied in two analgesic tests in rats: (1) vocalization threshold response; and (2) scored behavioral response to electric shock to the tail. Clomipramine (20-50 mg/kg i.p.) produced analgesia, decreasing behavioral response scores and increasing vocalization threshold. Morphine also reduced the response scores in the second test. Naloxone (0.8 mg/kg i.p) or methysergide (20 mg/kg i.p.) (no effect when given alone) abolished the analgesic effect of clomipramine as evaluated by vocalization threshold response. Naloxone alone (0.6 or 2 mg/kg i.p.) increased the behavioral response at 20 and 30 V but did not modify the score at 40 V. Naloxone reduced the analgesic effect of clomipramine or morphine in the behavioral test. These results suggest that the analgesic effect of clomipramine could involve both serotonergic and endorphin central systems.
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Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications' effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n=6), significant improvement in percent fluent speaking time (p=0.02) was found using a telephone task between baseline and pimozide (n=6), with average duration of dysfluencies significantly shorter (p=0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n=5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering.
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A 76-year-old patient, since the age of 45, presented with frequent attacks often triggered by emotional stimuli and characterised by forward head drop and a fall to the ground without loss of consciousness. Clinically these episodes were misinterpreted as pseudoseizures and treated with clomipramine for more than 20 years. In spite of this chronic therapy, during the last year, the attacks presented with a daily recurrence and, moreover, after arbitrary clomipramine withdrawal, they increased in frequency until they became subcontinuous. Videopolygraphic analysis, multiple sleep latency test (MSLT) and human leukocyte antigen (HLA) association studies were suggestive of narcolepsy and the recurrent episodes, diagnosed as status cataplecticus, recovered after citalopram administration.
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Methylphenidate (MPH), a psychostimulant used for treatment of attention deficit hyperactivity disorder (ADHD), is widely used by patients on antidepressants and methadone maintenance treatment (MMT). Preclinical studies showed MPH to exert analgesic effects when given alone or with morphine.
A retrospective review over a 4-year period of patients hospitalized in an intensive care unit who were diagnosed with BI; Mann-Whitney and Fischer's exact tests were used for comparisons.
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This paper describes the treatment of thirty-three patients who were suffering with obsessional symptoms and who were given the drug clomipramine (Anafranil, Geigy Pharmaceuticals). The symptoms were classified into phobic ruminations, non-phobic ruminations and rituals as well as into the less familiar group of normal and bizarre obsessions. Progress was assessed using the Shapiro card method and a brief description of this method is given. The results show that clomipramine possesses a specific anti-obsessional quality and that the use of this preparation is an effective treatment for obsessional patients. The paper also discusses certain aspects of therapy as well as suggesting an aetiological basis of obsessional symptoms.
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Shared psychotic disorder (folie à deux) is an uncommon entity reported mainly in the context of delusions. Obsessions and compulsions occur very rarely as shared psychopathology.
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To study the effect of cytochrome P-450 (CYP450) inhibitors on clomipramine (Clo) N-demethylation in vitro.