Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two multicenter, double-blind trials were conducted in adults with DSM-III (American Psychiatric Association 1980) defined Obsessive Compulsive Disorder (OCD), comparing clomipramine (Anafranil, CMI) up to 300 mg daily with placebo. Of 519 patients evaluated, 260 received CMI for up to 10 weeks. More than half of the CMI treated patients were significantly improved, approximately 30 percent were minimally improved, and 15 percent showed no improvement after CMI treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess treatment effects and attempts were made to correlate change in Y-BOCS score from baseline with a number of baseline characteristics, including age, sex, duration of OCD, baseline Y-BOCS score, baseline Hamilton Rating Scale for Depression (HAM-D) score, presence or absence of secondary depression, and predominance of obsessions or compulsions. Pearson and/or Spearman correlations failed to reveal any statistically significant correlations between outcome and any of the baseline characteristics studied. While the differences were not statistically significant, it did appear that male patients and patients with a longer duration of illness may be less likely to respond to CMI treatment; however, the overall conclusion from this analysis is that none of the variables studied is a reliable predictor of responses to treatment with CMI.
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PMID:Clinical predictors of treatment response in obsessive compulsive disorder: exploratory analyses from multicenter trials of clomipramine. 219 27

Clomipramine, a preferential inhibitor of 5-hydroxytryptamine uptake, has proven effective in the management of depression, resistant depression, and obsessive compulsive disorder. Investigators have also reported benefits of this medication in patients with phobia, panic disorder, chronic pain, Gilles de la Tourette's syndrome, premature ejaculation, anorexia nervosa, cataplexy, and enuresis. In double-blind studies of patients with depression, clomipramine has been significantly more effective than placebo and equivalent to standard tricyclics. Clomipramine is particularly well suited for the treatment of resistant depression, for which its efficacy may be enhanced by combination therapy with tryptophan and/or lithium. In at least 12 double-blind comparative trials, clomipramine has exhibited significant benefit in patients with obsessive compulsive disorder, this efficacy not being limited to patients with an associated depressive illness. In the United States, clomipramine is approved only for the treatment of obsessive compulsive disorder.
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PMID:Worldwide use of clomipramine. 219 35

1. Clomipramine has been found to be effective in the treatment of obsessive compulsive disorder (OCD) in nine placebo controlled studies whereas other conventional antidepressants lacking 5-HT reuptake inhibiting properties do not appear to be effective. 2. The placebo response rate in OCD is very low as is seen in the placebo controlled study of the efficacy of clomipramine 75mg in 14 patients suffering from OCD reported here. 3. Response appears early in treatment when compared with response of depression to antidepressants.
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PMID:Early response with clomipramine in obsessive compulsive disorder--a placebo controlled study. 229 52

Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semiselective serotonin uptake inhibitor, clomipramine. More recent studies directly comparing clomipramine with non-selective or norepinephrine-selective uptake inhibitors, such as desipramine or nortriptyline, as well as studies with new, more selective serotonin uptake inhibitors, including fluvoxamine and fluoxetine, have supported that hypothesis. Clomipramine's antiobsessional effect has been augmented with the serotonin precursor, L-tryptophan, or with lithium, which has prominent serotonergic effects. Patients whose OCD symptoms improved on clomipramine worsened when the drug was discontinued (regardless of duration of therapy) and improved when clomipramine was reinstituted. OCD symptoms also worsened when metergoline, a 5-HT antagonist, was given to patients who had improved with clomipramine. Metergoline given alone had no effect. Administration of m-chlorophenylpiperazine (m-CPP), a 5-HT receptor agonist, to untreated OCD patients increased their anxiety, depression, and dysphoria, and exacerbated their OC symptoms. After 4 months of clomipramine therapy, m-CPP failed to produce the same behavioural effects, suggesting an alteration of a 5-HT subsystem (possibly downregulation of some 5-HT receptors). The data reviewed suggest an important role for an abnormal brain 5-HT subsystem in patients with OCD.
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PMID:Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder. 269 36

Recent studies with clomipramine (CMI) have demonstrated that a pulse-loading approach is associated with a rapid improvement in symptomatology in the absence of continuous treatment. In the present study, sleep changes were evaluated to ascertain the rapidity of clomipramine's effect on electroencephalographic sleep, especially rapid eye movement (REM) and delta wave sleep measures. Clomipramine produced rapid changes in sleep with reduced sleep continuity and almost complete suppression of REM sleep as well as a redistribution of slow wave sleep. Delta waves during sleep were also found to be shifted to the earlier part of the night and increased in intensity. Spectral analysis revealed an increase in power in the delta frequency range that was correlated with clinical responsiveness. These studies point toward a role for clomipramine in the rapid treatment of depression and confirm that sleep physiology may be a good predictor of antidepressant action.
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PMID:Clomipramine and EEG sleep in depression. 269 1

Masked depression refers to a concept of a phenomenological state, either endogenous or psychogenic where somatic symptoms replace sadness: Thirty patients were evaluated by RDC (22 endogenous and 8 masked depressions) wherein in the latter dysphoria was replaced by a nonreactive persistent somatic complaint. They were rated on Beck and Hamilton Depression Scales, on Hamilton and Trait-State Anxiety Scales and the NOSIE. All patients presented with insomnia, anorexia, loss of weight, diminished libido and anhedonia. Initial ratings were similar for both diagnostic groups except for a significantly higher agitation factor and lower retardation in masked depression. Although 59.9 percent of the subjects are positive on the dexamethasone test, only 1 masked depression did not suppress secretion of cortisol. After a randomized 30-day drug trial where patients were assigned to Clomipramine or Desipramine, patients in both groups show significant improvement on rating scales but diagnostic group drug treatment interaction exists on anxiety and agitation criteria.
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PMID:[Comparison of masked and endogenous depression using psychometric scales, endocrinological markers and pharmacological responses. Masked depression versus endogenous depression]. 309 93

A double-blind comparative study of clomipramine and fluvoxamine was performed in 50 patients suffering from anxiety disorders (DSM-III). Patients were treated for 6 weeks with either 150 mg of clomipramine or 100 mg of fluvoxamine. The results show that both drugs at the dosages used are equipotent in reducing anxiety symptoms as assessed with the Hamilton Anxiety Scale and the Spielberger State-Trait Anxiety Inventory. Clomipramine differed from fluvoxamine in its efficacy with respect to associated depressive symptomatology in that it had a more pronounced effect on the Self Rating Depression Scale. The results support the hypothesis that brain serotonergic pathways are implicated in the pathophysiology of anxiety disorders, particularly in agoraphobia and panic disorders.
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PMID:Effect of serotonin uptake inhibitors in anxiety disorders; a double-blind comparison of clomipramine and fluvoxamine. 311 76

Fifty-six general practitioners, experienced in the use of diagnostic criteria from DSM III for affective and anxiety disorders, have taken part in a study involving 352 patients, 92 males (26%) and 260 females (74%) with an average age of 38.6 +/- 13.5. The epidemiologic part of this work consists in a case-control comparison of socio-demographic characteristics among subjects with panic disturbance and others unaffected with it. It allows to conclude that panic disturbance is two times more frequent in women than in men and most often in young people. The results of the therapeutic with Clomipramine at low dosage (40 mg) objective a complete removal of panic attacks in 21.5% and 64% of patients after a respectively 15 days treatment. Other criteria of evaluation (Hamilton Depression Rating scale--HDRS), Montgomery and Asberg Depression Scale--MADRS--, clinician's global assessment) evolve favorably also. It is however interesting to note that though it is not in originally more depressed patients that panic disturbance is most improved by treatment, there is on the other hand a correlation between scores from MADRS and HDRS and the number of panic attacks under treatment. These results corroborate the hypothesis that Clomipramine can be effective at low dosage in some patients with panic disturbance--here, slightly less than 2/3 of the cases--while for other patients higher dosages are necessary.
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PMID:[Panic disorder in general medicine. Epidemiological data and treatment with clomipramine]. 321 39

Clomipramine, administered to neonatal rats, has been reported to produce adult behavioral and REM sleep abnormalities. They include decreased sexual behavior, increased ambulation in the outer part of an open-field arena, increased REM sleep % of total sleep time, and in descriptive data, short REM latency, and increased REM phasic events. Since these abnormalities resemble some found in human endogenous depression, we have hypothesized that the adult rats represent an animal model of depression. Diminished aggressive behavior is a common characteristic of endogenous depression. This study tested the validity of the animal depression model by determining in rats the effect of neonatal clomipramine on adult shock-induced fighting. Experimental rats were treated neonatally with clomipramine and control rats were treated neonatally with saline. When they matured, compared with control rats, experimental rats had significantly fewer offensive fighting responses, and significantly more defensive fighting responses. The findings add some support to the validity of the animal depression model produced by neonatal clomipramine.
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PMID:Animal depression model by neonatal clomipramine: reduction of shock induced aggression. 325 40

The efficacy of clomipramine hydrochloride in the treatment of agoraphobia was investigated in an eight-week placebo-controlled double-blind study. One hundred eight women diagnosed as agoraphobic by DSM-III guidelines were randomly assigned to the clomipramine or placebo group; 70 women (mean age, 36.6 years) completed the eight-week trial. The study medication was prescribed on the basis of weekly increments to a maximum of 300 mg/d, with a mean dosage at week 8 in the clomipramine hydrochloride group of 82.8 mg/d. Assessments performed prior to the trial and at the four- and eight-week points included the completion of standardized questionnaires and daily diaries, as well as the administration of a Behavioral Approach Test. Clomipramine was significantly superior to the placebo on several indexes of phobic symptoms and on measures of depression and dysphoria. Results are discussed in terms of the hypothesized action of clomipramine and the pattern of significant findings.
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PMID:Clomipramine treatment of agoraphobic women. An eight-week controlled trial. 328 81


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