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)

Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD.
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PMID:A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. 885 97

This article is a practical review of the current psychopharmacological agents used in the treatment of child and adolescent psychiatric disorders. Psychostimulants such as methylphenidate, dexamphetamine and pemoline are effective in the control of symptoms associated with attention deficit hyperactivity disorder. The controlled release preparations and the adjunctive use of clonidine are helpful to extend stimulant effects and control adverse effects. Tricyclic antidepressants are helpful in individual cases of child and adolescent depression, but adverse effects may limit their use. Clomipramine has been found to be effective for childhood obsessive-compulsive disorder. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) appear to be safer for depression and are also useful in obsessive-compulsive disorder. Buspirone is effective for the treatment of anxiety disorders in children. Newer atypical antipsychotics such as risperidone may have less limiting adverse effects than older antipsychotics in the treatment of psychosis and severe behaviour disorders, but the physician must be vigilant for the emergence of tardive dyskinesia. Drug treatment in children and adolescents must take into account the child's environmental influences and be part of an overall treatment plan where individual, familial and cultural issues are addressed.
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PMID:Pharmacological treatment of psychiatric disorders in children and adolescents: focus on guidelines for the primary care practitioner. 886 45

The effects of neonatal treatment with clomipramine on the sensitivity of cholinergic receptor and passive avoidance behavior were studied to examine the activity of the central cholinergic system. Rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.) and at 3 months of age the thermic responses to three different doses of oxotremorine were measured. One day following oxotremorine challenge study, the animals were subjected to passive avoidance training and retention was measured 24-hr later. Clomipramine treated animals showed an enhanced cholinomimetic-induced hypothermia and an increased latency in passive avoidance test. These findings may reflect an altered sensitivity of central cholinergic system in rats given clomipramine as neonates. The results were compared to other animal models of depression.
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PMID:Effects of neonatal clomipramine on cholinergic receptor sensitivity and passive avoidance behavior in adult rats. 896 88

Obsessive-compulsive disorder (OCD) has been successfully treated with proserotonergic agents for some years. Clomipramine was the first drug used, but several clinical trials have been conducted more recently to assess the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to compare the antiobsessional efficacy of three SSRIs, fluvoxamine, paroxetine, and citalopram. Thirty obsessive-compulsive patients without comorbid axis I diagnoses except for tic disorder as assessed by DSM-III-R criteria gave informed consent and were recruited consecutively; they underwent a 10-week randomized treatment with fluvoxamine, paroxetine, or citalopram. Ratings were performed under blind conditions every 2 weeks from baseline to the end of the study and by the Yale-Brown Obsessive-Compulsive Scale, the National Institute of Mental Health-Obsessive-Compulsive Scale, the Clinical Global Impressions Scale, and the Hamilton Rating Scale for Depression. Quantitative and qualitative analyses of the antiobsessional efficacy of the three drugs were completed with analysis of variance with repeated measures and survival analysis. The results showed no significant differences between the three treatments. The preliminary conclusions drawn from this study concern the interchangeable antiobsessional effects of different SSRIs, although further studies of "cross-response" to these drugs are needed.
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PMID:Efficacy of fluvoxamine, paroxetine, and citalopram in the treatment of obsessive-compulsive disorder: a single-blind study. 924 Oct 5

Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10-134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5-15 mg/kg b. i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.
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PMID:Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression? 940 8

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

Clomipramine (CLI), a REM sleep suppressant, alleviates symptoms of depression in adults but produces depressive behaviors if applied neonatally. Both effects of CLI as applied to adults and to neonates have been interpreted as consequences of its involvement in REM sleep deprivation. However, the paradox of these conflicting effects remains to be understood. The current study attempts to find the possible answer by studying the effects of CLI on postnatal sleep. Eight postnatal rats were evaluated polysomnographically for nine days. Four rats were treated with CLI, 40 mg/kg/day for six days, and four rats were treated with equivolume saline during the same period. The results showed that 1) CLI treatment did not reduce the time of phasic muscle activity which appears during slow wave EEG as it did during REM sleep; 2) during treatment, rats treated with CLI had 44.66%-68.62% REM sleep reduction, varied according to age; 3) REM sleep reduction during treatment was generally compensated by non-REM sleep, so that total sleep (and wakefulness) was comparable to that experienced by rats treated with saline; 4) an obvious REM sleep rebound was observed after drug withdrawal at the age of P19. These results suggest that 1) the stage that shows phasic muscle activity simultaneously with a high amplitude EEG is not REM sleep and is likely to be independent from non-REM sleep in terms of the percentile change; 2) REM sleep reduction without a corresponding increase in wakefulness in postnatal rats is likely the mediator of postnatal RSD in the production of adult depression; and 3) the neuronal bases responsible for REM rebound function by the end of the postnatal third week.
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PMID:Clomipramine suppresses postnatal REM sleep without increasing wakefulness: implications for the production of depressive behaviors. 1190 26

Postnatal treatment between 8 to 21 days of age with clomipramine (15 mg/kg, twice daily) produces an animal model that has many of the behavioral hallmarks of depression. In this study, we investigated the enduring behavioral and neurochemical effects of this early treatment in adult animals. Locomotor activity was increased in clomipramine-treated males, but not females, relative to vehicle-treated subjects. Increases in anxiety-like behavior in the elevated plus maze also were observed in clomipramine-exposed adults, but no sex differences were detected. Clomipramine-treated animals had shifts in the laterality of monoamines in limbic regions with lower serotonin levels on the right side while vehicle-treated animals had lower serotonin on the left side. The lateralization of dopamine content demonstrated the same pattern. This decline in monoaminergic content is consistent with clinical studies demonstrating decrements in serotonin as well as alterations in the lateralization of function in individuals with major depressive order.
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PMID:Differences in behavior and monoamine laterality following neonatal clomipramine treatment. 1211 90

The action of the tricyclic antidepressant clomipramine on membrane currents elicited by acetylcholine was studied in Xenopus oocytes expressing neuronal alpha2beta4 nicotinic acetylcholine receptors. Clomipramine inhibited the acetylcholine responses rapidly and reversibly, with a similar IC(50) when the oocytes were preincubated with clomipramine (1.3+/-0.2 microM) or when they were exposed simultaneously with acetylcholine and clomipramine (1.5+/-0.3 microM). The EC(50) was 39.9+/-2.1 microM for acetylcholine alone and 65.7+/-3.6 microM for acetylcholine in the presence of 2 microM clomipramine. The inhibitory effect of clomipramine was weakly voltage-dependent, with an electric distance of approximately 0.14. Moreover, clomipramine increased the rate of decay of currents elicited by acetylcholine. From all of these, we conclude that clomipramine reversibly and noncompetitively regulates neuronal alpha2beta4 nicotinic acetylcholine receptors by blocking the open receptor-channel complex at a site close to the extracellular vestibule of the channel. The actions of clomipramine on neuronal nicotinic acetylcholine receptors may play an important role in the treatment of mental depression and other mood disorders.
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PMID:Effects of clomipramine on neuronal nicotinic acetylcholine receptors. 1219 77

From a clinical point of view, orthostatic hypotension is a significant side effect during antidepressant treatment, particularly in the case of tricyclic antidepressants (TCAs). This prospective, randomized clinical trial evaluated the effects of clomipramine and moclobemide on orthostatic blood pressure during treatment for depression. One hundred and fifteen depressed inpatients, age up to 70 years, were randomized to treatment with either moclobemide (400 mg/day) or clomipramine (150 mg/day) after 1 week of placebo treatment. Orthostatic blood pressure was measured weekly over the 6-week study period. Clomipramine, but not moclobemide, caused a statistically significant fall in systolic (F = 9.37, P = 0.0037) and diastolic orthostatic blood pressure (F = 3.74, P = 0.0017). In the clomipramine-treated group of patients, we found no correlation between subjective complaints of orthostatic dizziness and the size of systolic orthostatic blood pressure. In conclusion, this study indicates that moclobemide does not induce orthostatic side effects, which is a significant problem in treatment with TCAs. However, the choice of antidepressants depends on other factors as well, e.g. the therapeutic efficacy.
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PMID:Orthostatic side effects of clomipramine and moclobemide during treatment for depression. 1619 34


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