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)

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosage of clomipramine hydrochloride are described, and clinical studies of the use of clomipramine in treating obsessive-compulsive disorder (OCD), other psychiatric conditions, and chronic pain are reviewed. Clomipramine hydrochloride, a tricyclic antidepressant, is a potent inhibitor of serotonin reuptake and may affect dopaminergic neurotransmission, suppress rapid eye movement sleep, produce changes in electrocardiograms, and elevate plasma prolactin. The drug is well absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism. Peak plasma concentrations occur three to four hours after a 150-mg oral dose. The mean elimination half-life is 39 hours. Some 66% of a dose is excreted in the urine, the remainder being eliminated in the feces. In clinical trials, clomipramine was significantly more effective than placebo, clorgiline, amitriptyline, imipramine, and doxepin in ameliorating the symptoms of OCD. Initial effects are seen at four weeks; improvement may continue for up to 18 weeks. Clomipramine may also be effective in treating panic attacks, phobias, depression, and chronic pain. The most common adverse effects of clomipramine are anticholinergic; others include nausea, seizures, and sexual difficulties. Interactions between clomipramine and barbiturates, haloperidol, monoamine oxidase inhibitors, and cigarette smoking have been documented. The usual initial adult dosage is 25-50 mg/day, titrated gradually to 250 mg/day if necessary. Clomipramine hydrochloride is a welcome new agent for the treatment of obsessive-compulsive disorder. Although its adverse-effect profile is like that of other tricyclic antidepressants, sexual dysfunction and seizures may be more frequent with this agent and limit its use.
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PMID:Clomipramine: an antiobsessional tricyclic antidepressant. 218 Jun 23

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

Intravenous infusions of clomipramine and maprotiline, preceded by a five-day tranquilising regimen with a neuroleptic drug, were given to 177 patients with treatment-resistant depression. During the treatment period of 10-20 days the patients were given one infusion daily followed by both antidepressants taken orally. The neuroleptic drug was given at night, from the start of the infusion phase to the end of hospitalisation. After four weeks 66% of the endogenous depressions and 53% of the exhaustion depressions had completely regressed. In patients who failed to respond the infusion regimen can be repeated, if necessary with nomifensin (Alival) instead of clomipramine (Anafranil) and maprotiline (Ludiomil) in order to achieve the desired improvement without ECT. In addition to careful diagnosis, a prerequisite for likely success in the management of treatment-resistant depression is the combination of drug administration with adequate psychotherapeutic and physiotherapeutic measures. The infusion regimen is relatively easy to undertake, can also be used on an out-patient basis and could be the treatment of choice in the future, not only for treatment-resistant depressions but also for patients whose depressive state requires rapidly effective antidepressive measures.
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PMID:[Management of treatment-resistant depression without ECT (author's transl)]. 611 26

A double-blind, randomized trial is described which was designed to compare the clinical effect of 100 mg daily of maprotiline (Ludiomil) and of clomipramine (Anafranil) given by the intravenous route in forty hospitalized female patients with severe and resistant primary depression. Physicians' assessment of patients' progress was made following 5, 9 and 21 days of treatment. The response rates to maprotiline and clomipramine were not significantly different even if a greater number of patients responded to clomipramine. None of the demographic and clinical variables considered could be identified as factor predicting the response to maprotiline and to clomipramine, even if a trend for a preferential responsiveness to clomipramine in the older patients was observed.
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PMID:Intravenous maprotiline in severe and resistant primary depression: a double-blind comparison with clomipramine. 634 54

Forty-two patients aged between 19 and 70 years (30 women and 12 men) suffering from primary unipolar depression were randomly selected and treated under double-blind conditions with either mianserin (Lantanon; Organon) or clomipramine (Anafranil; Ciba-Geigy) after an initial wash-out period. Patients on all other medication, including benzodiazepines, were excluded from the study. The severity of depression was assessed on day 0 and after 1, 2, 3, 4 and 5 weeks' treatment. There were no significant pretrial differences between the groups in respect of severity of depression, age, sex or previous psychiatric history. During the 1st week of treatment all subjects received either mianserin 30 mg or clomipramine 75 mg once daily. From the 2nd week onwards the dose was doubled. Thirty patients completed the trial, 16 on mianserin and 14 on clomipramine. The improvement on both treatments was marked, favouring mianserin but only reaching significance in the 5th week. Side-effects, especially tremor, tachycardia, dystonia, dizziness, excitement, nasal congestion and dry mouth, were significantly more common in the group using clomipramine. This study confirms reports that mianserin is an effective antidepressant which is better tolerated and produces fewer side-effects (especially anticholinergic) than comparable tricyclic antidepressants such as clomipramine.
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PMID:Mianserin and clomipramine in the treatment of depression. 704 54

A technique for assay of clomipramine (Anafranil) and its demethylated metabolite by high performance liquid chromatography is described in this study. This technique utilizes an XoA 800 normal phase column and a quaternary solvent composed of dietylamine, water, acetonitrile, and ethanol. Plasma of patients was extracted with hexane in an alkaline medium (pH 10). The use of an internal standard seemed to improve the assay's repeatability. The simplicity and rapidity of this technique should make it a useful aid for determining optimal doses of Anafranil for patients with depression.
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PMID:[Plasma assay of clomipramine and demethylclomipramine by high performance liquid chromatography]. 714 51

The antidepressants clomipramine hydrochloride (Anafranil), fluoxetine hydrochloride (Prozac), and sertraline hydrochloride (Zoloft) are the main choices for pharmacologic treatment of obsessive-compulsive disorder. Often, drug doses for obsessive-compulsive disorder are higher than for depression, and improvement occurs more slowly and is often only partial. Behavior therapy involving exposure to feared objects or situations and prevention of ritualistic behavior complements pharmacologic treatment. Referral to a behavioral therapist may be necessary to achieve recovery.
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PMID:Obsessive-compulsive disorder. How to free patients from intrusive thoughts and rituals. 799 73

The objective of this study was to evaluate the mode of prescription and the users of antidepressant agents. It consisted of an initial phase (survey of the general population), aimed at selecting a representative sample of antidepressants users by a mail questionnaire, without asking prescribers in order to avoid the bias inherent to such an approach. Results showed a current incidence of use of 2.75 % for the 8 main antidepressants, i.e. more than one million adults in France. The distribution of antidepressants showed Prozac in first place, followed by Anafranil, and Laroxyl, then Stablon, Athymil, Survector and Ludiomil. In more than 50 % of cases, antidepressants have been taken for a year or more, continuously of intermittently. They were prescribed by a general practitioner in 60 % of cases and a psychiatrist in 30 %. A second survey phase (telephone) undertaken by psychiatrists and involving a sample of this population enabled determination of the pathophysiological profile of consumers at the time of prescription of antidepressant treatment, using a validated diagnostic tool, the MINI. Taking all drugs together, results showed that prescription was within Marketing Authorization approved indications in about 65 % of cases (existence of depression 61 %, dysthymia 3 %, OCD 1 %). This study shows that, in 23 % of cases, antidepressants are not used in patients with one of the psychiatric diseases identified by the MINI but nevertheless suffering from pathophysiological symptoms (subsyndronic syndrome). It can be concluded that, in some subjects, antidepressants are used in non-identified disorders. It must also be recognized that, with 3 % of users, the population of individuals treated by antidepressants is less than that of patients suffering, in the general population, from depression (5 to 10 % per year, according to studies).
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PMID:[Pharmaco-epidemiologic study of the use of antidepressant drugs in the general population]. 876 26

Obsessive compulsive disorder (OCD) is characterized by recurrent and intrusive thoughts that are distressing (obsessions) and/or repetitive behaviors or mental acts that the person feels driven to perform (compulsions). OCD has a partly genetic basis. For treatment of OCD, potent serotonin reuptake inhibitor (SRI) drugs (clomipramine (Anafranil), fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)), which act on the serotonin transporter protein, are uniquely efficacious. A polymorphism in the promoter region of the gene (SLC6A4) encoding this protein, was recently reported to affect protein expression and to be associated with measures of anxiety and depression and with autism (using a family-controlled transmission disequilibrium test (TDT) design). SLC6A4 therefore has strong a priori support for potentially influencing risk for OCD: the protein it encodes is a medication target; a polymorphism in the gene affects function; and that polymorphism has been shown to be associated with behavioral phenotypes. We used the TDT with a set of 34 European-American family trios, 30 unrelated and four drawn from an extended pedigree, to test for linkage disequilibrium between OCD and alleles at the SLC6A4 promoter polymorphic locus. Of 35 heterozygous parents, 24 transmitted the 'l' SLC6A4 allele and 11 transmitted the 's' allele (chi 2 TDT = 4.83; P < 0.03). Considering only the 13 SRI drug nonresponders, there were 13 heterozygous parents, of whom 10 transmitted the 'l' allele and three the 's' allele (chi 2 TDT = 3.77; P < 0.052). These data provide preliminary support for association and linkage disequilibrium between the SLC6A4 'l' allele and OCD.
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PMID:Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. 967 4

Recent studies suggest several problems associated with selective serotonin reuptake inhibitors (SSRIs) when administered during pregnancy. During organogenesis, paroxetine (Deroxat, Paxil, or generics) was associated with a significantly increased risk of major congenital malformations. Such an increase had already been reported with clomipramine (Anafranil), a tricyclic antidepressant. After the time of organogenesis, SSRIs have also been associated to risks. Of these, the more frequent is neonatal toxicity, while pulmonary hypertension in the newborn is likely to be the more severe. These newly discovered side effects arouse questions about the treatment of depression during pregnancy.
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PMID:[Selective serotonin reuptake inhibitors (SSRIs) in pregnancy]. 1668 31


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