Chagas infection is a major endemic disease affecting Latin American countries. The persistence of Trypanosoma cruzi generates a chronic inflammatory reactivity that induces an immune response directed to the host's tissues. The effectiveness of the treatment in the chronic phase is still unsatisfactory due, amongst other reasons, to the collateral effects of the drugs used. We investigated the effect of clomipramine, a tricyclic antidepressant that, when used as a treatment of T. cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive and vital enzyme of T. cruzi. Clomipramine improved survival (P<0.05) by diminishing the parasite intensity as demonstrated by PCR studies in the heart and skeletal muscle, and significantly prevented the evolution to fibrosis of the inflammatory infiltrates. Clomipramine could be a good candidate for the treatment of chronic Chagas disease.

BACKGROUND:

There is growing evidence that memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, may be applied as an add-on in treating patients suffering from obsessive-compulsive disorders (OCD). The aim of the present study was therefore to assess the effect of adjuvant memantine in a double-blind, randomized, and placebo-controlled study of the treatment of patients suffering from OCD.

METHOD:

A total of 40 inpatients (32 females (80 %); mean age = 31.25 years) suffering from OCD were randomly assigned to a treatment (administration of memantine) or a control group (placebo). Treatment lasted for 12 consecutive weeks. All patients were treated with selective serotonin re-uptake inhibitors or clomipramine. Patients completed the Yale-Brown Obsessive Compulsive Scale four times. Experts' ratings consisted in clinical global impression (clinical global impressions (CGI), illness severity and illness improvement; two to three times). Liver enzymes SGOT and SGPT were also assessed (twice).

RESULTS:

Of the 40 inpatients approached, 29 completed the 12 consecutive weeks of the study. Of the 11 dropouts, 6 were in the target group and five in the control group. Symptoms significantly decreased across the period of the study, but particularly in the treatment compared with the control group (significant time × group interaction). Illness severity (CGI severity) also significantly decreased over time but more so in the treatment than in the control group (significant time × group interaction). Illness improvements (CGI improvements) were not significant.

CONCLUSIONS:

The pattern of results from the present double-blind, randomized, and placebo-controlled study for the treatment of patients suffering from OCD suggests that adjuvant memantine does significantly and favorably impact on OCD.

Introduction: Obsessive-compulsive disorder (OCD) affects the daily life of the patients. Chronic nature of this disease and the need for long-term high-dose drug therapy for its maintenance increase the risk of metabolic and toxicological complications. Areas covered: In this concise article, the metabolic and toxicological aspects of major medication categories prescribed in OCD, such as serotonin-specific reuptake inhibitors, tricyclic antidepressant (clomipramine), serotonin-norepinephrine reuptake inhibitors, and atypical antipsychotics indicated in OCD (both Food and Drug Administration-approved and off-label) are discussed. Expert opinion: The most critical point in pharmacotherapy of OCD is the need for the high-dose and long-term use of drugs. In OCD, generally the higher doses of applicable drugs than those used in depression are required, often exceeding the recommended maximum dose. Moreover, such high doses should be given for at least 10 - 12 weeks to ensure the adequate treatment duration for the clinical effects to emerge. This long-term high-dose maintenance therapy increases the risk of drug toxicity and adverse effects. Physicians should take extra care in periodical assessment of signs and symptoms of metabolic and toxicological complications in patients. Subjective symptoms reported by patients should be carefully assessed and not attributed to obsessive nature of the patients.

Background:

Non-rapid-eye-movement parasomnias or disorders of arousal (DOA) are more prevalent in children, but they do occur in adults. There are no practice parameters published for treatment of DOAs.

Methods:

After obtaining institutional review board approval, an electronic search was conducted for ICD9 codes related to DOAs in our clinic databases. The resulting charts were reviewed by the authors for accuracy, and 103 out of 232 were included in the final analysis.

Results:

Sleepwalking is the most common DOA presentation. Treatment with low-dose clonazepam has a response rate of 73.7%. Cognitive behavioral therapy (CBT) for insomnia, sertraline, clomipramine and temazepam may also be effective alternatives.

Conclusion:

DOAs respond to benzodiazepines, antidepressants and CBT. Large, randomized trials are needed to further assess these therapeutic alternatives.

The subjective measures used to study mood disorders in humans cannot be replicated in animals; however, the increasing application of objective neuropsychological methods provides opportunities to develop translational animal tasks. Here we describe a novel behavioral approach, which has enabled us to investigate similar affective biases in rodents. In our affective bias test (ABT), rats encounter two independent positive experiences-the association between food reward and specific digging substrate-during discrimination learning sessions. These are performed on separate days under either neutral conditions or during a pharmacological or affective state manipulation. Affective bias is then quantified using a preference test where both previously rewarded substrates are presented together and the rat's choices recorded. The absolute value of the experience is kept consistent and all other factors are counterbalanced so that any bias at recall can be attributed to treatment. Replicating previous findings from studies in healthy volunteers, we observe significant positive affective biases following acute treatment with typical (fluoxetine, citalopram, reboxetine, venlafaxine, clomipramine) and atypical antidepressants (agomelatine, mirtazapine), and significant negative affective biases following treatment with drugs associated with inducing negative affective states in humans (FG7142, rimonabant, 13-cis retinoic acid). We also observed that acute psychosocial stress and environmental enrichment induce significant negative and positive affective biases, respectively, and provide evidence that these affective biases involve memory consolidation. The positive and negative affective biases induced in our test also mirror the antidepressant and pro-depressant effects of these drugs in patients suggesting our test has both translational and predictive validity. Our results suggest that cognitive affective biases could contribute to drug- or stress-induced mood changes in people and support the hypothesis that a cognitive neuropsychological mechanism contributes to antidepressant drug efficacy.Neuropsychopharmacology advance online publication, 17 April 2013; doi:10.1038/npp.2013.69.

Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimental Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. Infected mice were treated with CLO 5mg/kg/day and BZN 50 and 100mg/kg/day, each separately or together. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopathological studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly (P<0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The lower dose of BZN (50mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of BZN (100mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO presented lesser side effects than the treatment with BZN.

Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.

OBJECTIVE:

Aquagenic pruritus is the development of severe, prickling-like skin discomfort without observable skin lesions that is evoked by contact with water at any temperature.

METHOD:

This is a case report of a man presenting with aquagenic pruritus after starting clomipramine treatment for anxiety and depression.

RESULTS:

The patient's aquagenic pruritus resolved after discontinuing the clomipramine but reemerged when treatment was restarted.

CONCLUSIONS:

A greater awareness and knowledge about aquagenic pruritus among physicians could help improve the clinical recognition and management of this clinical entity.

Amitriptyline.HCl (AMI) and clomipramine.HCl (CMI) react with eosin Y (EY) in pH 3.8 NaAc-AcH buffer solution to form ion association complex which results in quenching of fluorescence of EY and appearance of a new resonance Rayleigh scattering (RSS) spectrum at 620 nm. The spectral characteristics of absorption, fluorescence and RSS spectra have been investigated. The factors influencing the reaction were studied and optimum conditions for the reaction have been determined. Based on fluorescence quenching, a simple and sensitive spectrofluorimetric method for determination of AMI and CMI has been developed. The fluorescence quenching intensity was measured at 550 nm using an excitation wavelength of 310 nm. The calibration graph was found to be rectilinear in the range 0.08-2.0 μg mL(-1) with detection limit of 0.017 μg mL(-1) for AMI and 0.06-2.0 μg mL(-1) with detection limit of 0.015 μg mL(-1) for CMI. The method can be satisfactorily applied to the determination of AMI and CMI in tablets without interference from commonly occurring exicipients. The recovery and RSD values obtained indicate good accuracy and precision of the method. The mechanism of the reaction and fluorescence quenching has also been discussed.

Tricyclic antidepressants are used in the treatment of various pain syndromes. The antidepressant clomipramine inhibits predominantly the reuptake of serotonin in the central nervous system. The mechanism of its analgesic effect is not fully understood. The AIM of the present study was to find experimentally any dose-effect dependence in the analgesic effect of clomipramine and the involvement of the 5-HT2 and 5-HT3 receptors in the mechanism of this effect.Fifty male Wistar rats were used in the study allocated to five groups (10 animals each): a saline treated control group, one positive control group treated with metamizole and three experimental groups treated with intraperitoneally administered clomipramine in doses of 5, 10 and 20 mg/kg bw, respectively. To study the role of 5-HT2 and 5-HT3 receptors in this effect we used another five groups (10 animals each): control, positive control and three experimental groups treated with clomipramine only, clomipramine and granisetrone and clomipramine and cyproheptadine, respectively. Three nociceptive tests were used: the hot plate test, analgesimeter and the acetic acid-induced writhing test. To gauge the antinociceptive action we used the increased latency in the hot plate test expressed as maximum possible effect % (%MPE), the increase in paw pressure to withdraw the hind paw in analgesimeter and decrease in the number of spinal cord writhes in the acetic acid test.Clomipramine in a dose of 20 mg/kg bw significantly increased the %MPE in hot plate test and the pressure to withdraw the hind paw in the analgesimeter when compared with the control. In the acetic acid test clomipramine decreased non-significantly the number of writhes compared with the controls. Granisetrone reduced non-significantly the antinociceptive effect of clomipramine in all tests. Cyproheptadine potentiated the analgesic effect of clomipramine in acetic acid test and decreased it significantly in the hot plate test. In analgesimeter cyproheptadine decreased significantly the paw pressure to withdraw the tested hind paw at 1 hour and non-significantly at 2 hours.Clomipramine in the dose of 20 mg/kg bw has a pronounced antinociceptive affect towards thermal and mechanical pain stimulation. The 5-HT2 and 5-HT3 receptor subtypes are very likely involved in the mechanism of this effect.