Biomedical subjects

M S Lima

Publications and source records attributed to M S Lima.

At least 19 recordsLinked to original sources

PubMed2007

Crack cocaine: a five-year follow-up study of treated patients.

OBJECTIVES: To follow-up a group of 131 crack cocaine users and examine drug use, treatment experience, employment status, involvement in crime and mortality at 2 and 5 years. METHODS: Consecutive crack-dependent patients who were admitted to a detoxification unit in São Paulo between 1992 and 1994 were re-interviewed on two occasions: 1995-1996 and 1998-1999. RESULTS: 5 years after treatment information was obtained on 124 (95%) of the original cohort. 39.7% (n = 52) of the patients reported having been abstinent from cocaine for at least the last year, and 21.4% (n = 28) had used the drug. Of those subjects not using cocaine at 2 years, 19 (62%) were still abstinent at 5 years. Twenty-three (17.6%) patients had died by the 5-year follow-up with homicide, due to firearms or other weapons, being the commonest cause (n = 13). The annual adjusted mortality rate for the sample was 24.92 deaths/1,000 individuals, the excess mortality rate was of 21.64 deaths/1,000 individuals, and the standardized mortality ratio was 7.60. A history of injecting drug use, unemployment at the time of the index admission and administrative discharge at the index admission were factors that contributed to the risk of dying over the next 5 years. CONCLUSIONS: There was a progressive movement towards abstinence over the follow-up period, and there was evidence that once abstinence had been achieved it was maintained. On the other hand, the mortality rate was extremely high and was higher among those who were still using crack at 2 years.

Adolescent↗

PubMed2006

Penfluridol for schizophrenia.

BACKGROUND: Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it is administered once a week. OBJECTIVES: To review the effects of penfluridol for treatment of those with schizophrenia and schizophrenia-like illnesses in comparison to placebo, other antipsychotic medication or no intervention. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's Register (2005), the Cochrane Central Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched references of all identified studies and sought citations of these studies in the Science Citation Index. We contacted the authors of trials and the manufacturer of penfluridol. SELECTION CRITERIA: We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS: We independently extracted and analysed data on an intention-to-treat basis. We calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat. We calculated weighted mean differences (WMD) for continuous data. MAIN RESULTS: We included twenty-five studies with a total of 1024 participants. Most of these studies were undertaken in the 1970s when penfluridol was launched. Ten studies, with 365 patients, compared penfluridol to placebo. In the meta-analysis of medium-term lasting studies, penfluridol was superior to placebo in the main efficacy measures: 'improvement in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and 'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3 CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to penfluridol or oral typical antipsychotics. There were no particular differences between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine, thioridazine, or thiothixene for the main outcome measures in medium-term trials: 'improvement on global state' (N=2 studies), 'leaving the study early' (N=6), 'needing additional antipsychotic' (N=3), needing antiparkinsonian medication (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to depot typical antipsychotics. In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50). AUTHORS' CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The efficacy and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for chronic sufferers of schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention.

Antipsychotic Agents↗

PubMed2006

Antidepressants for anorexia nervosa.

BACKGROUND: Anorexia Nervosa (AN) is an illness characterised by extreme concern about body weight and shape, severe self-imposed weight loss, and endocrine dysfunction. In spite of its high mortality, morbidity and chronicity, there are few intervention studies on the subject. OBJECTIVES: The aim of this review was to evaluate the efficacy and acceptability of antidepressant drugs in the treatment of acute AN. SEARCH STRATEGY: The strategy comprised of database searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, MEDLINE (1966 to April 28th, 2005), EMBASE (1980 to week 36, 2004), PsycINFO (1969 to August week 5, 2004), handsearching the International Journal of Eating Disorders and searching the reference lists of all papers selected. Personal letters were sent to researchers in the field requesting information on unpublished or in-progress trials. SELECTION CRITERIA: All randomised controlled trials of antidepressant treatment for AN patients, as defined by the Diagnostic and Statistical Manual, fourth edition (DSM-IV) or similar international criteria, were selected. DATA COLLECTION AND ANALYSIS: Quality ratings were made giving consideration to the strong relationship between allocation concealment and potential for bias in the results; studies meeting criteria A and B were included. Trials were excluded if non-completion rates were above 50%. The standardised mean difference and relative risk were used for continuous data and dichotomous data comparisons, respectively. Whenever possible, analyses were performed according to intention-to-treat principles. Heterogeneity was tested with the I-squared statistic. Weight change was the primary outcome. Secondary outcomes were severity of eating disorder, depression and anxiety symptoms, and global clinical state. Acceptability of treatment was evaluated by considering non-completion rates. MAIN RESULTS: Only seven studies were included. Major methodological limitations such as small trial size and large confidence intervals decreased the power of the studies to detect differences between treatments, and meta-analysis of data was not possible for the majority of outcomes. Four placebo-controlled trials did not find evidence that antidepressants improved weight gain, eating disorder or associated psychopathology. Isolated findings, favouring amineptine and nortriptyline, emerged from the antidepressant versus antidepressant comparisons, but cannot be conceived as evidence of efficacy of a specific drug or class of antidepressant in light of the findings from the placebo comparisons. Non-completion rates were similar between the compared groups. AUTHORS' CONCLUSIONS: A lack of quality information precludes us from drawing definite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice.

Anorexia Nervosa↗

PubMed2004

Trifluoperazine for schizophrenia.

BACKGROUND: Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses. OBJECTIVES: To estimate the effects of trifluoperazine compared with placebo and other drugs. SEARCH STRATEGY: Searches of the Cochrane Schizophrenia Group's register of trials (March 2002), supplemented with hand searching, reference searching, personal communication and contact with industry. SELECTION CRITERIA: All clinical randomised trials involving people with schizophrenia and comparing trifluoperazine with any other treatment. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and quality rated and data was extracted. For dichotomous data, relative risks (RR) were estimated, with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, the number needed to treat (NNT) was calculated. We estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS: 1162 people from 13 studies were randomised to trifluoperazine or placebo. For global improvement, small short-term studies favoured trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between trifluoperazine and the atypical drug, sulpiride. REVIEWER'S CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence.

Antipsychotic Agents↗

PubMed2003

Antidepressants for generalized anxiety disorder.

BACKGROUND: Pharmacological treatments have been successfully used to treat Generalized Anxiety Disorder (GAD). The mainstay for the pharmacological treatment of GAD in past decades has been the use of benzodiazepine and non benzodiazepine anxiolytics. Data emerging over the last two decades have shown that antidepressants may be equally effective to anxiolytics for treating GAD. The use of antidepressants for treating GAD may be advantageous, due to the fact that GAD presents a high co morbidity ratio with major depressive disorder (62%) and dysthymia (37%). OBJECTIVES: To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder. SEARCH STRATEGY: Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal communication; conference abstracts and book chapters on the treatment of generalized anxiety disorder. SELECTION CRITERIA: Randomised controlled trials were included. Exclusion criteria were: non randomised studies; studies which included patients with generalized anxiety disorder and another Axis I co-morbidity. DATA COLLECTION AND ANALYSIS: The data from studies were extracted independently by two reviewers and relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. MAIN RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating GAD. The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not differ between antidepressants. Only one study presented data on imipramine and trazodone. Imipramine was chosen as the reference drug and, therefore, data on trazodone could not be included in the meta analysis. Only one study was conducted among children and adolescents (Rynn 2001). The latter study showed very promising results of sertraline in children and adolescents with GAD, which warrants its replication in larger samples. REVIEWER'S CONCLUSIONS: The available evidence suggests that antidepressants are superior to placebo in treating GAD. There is evidence from one trial suggesting that paroxetine and imipramine have a similar efficacy and tolerability. There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients. Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients.

Antidepressive Agents↗

PubMed2003

Inflammatory responses induced in mice by lectin from Talisia esculenta seeds.

A novel lectin from Talisia esculenta seeds (TEL) has recently been purified and characterized. In this study we investigated the proinflammatory activity of TEL in mice using both the air-pouch and peritoneal cavity as well as paw oedema models. TEL (10-40 microg) induced significant neutrophil and mononuclear cell recruitment when injected into either mouse air-pouch or peritoneal cavity. The neutrophil accumulation into the air-pouch was dose- and time-dependent with a maximal response at 16 h, returning to control levels at 72 h whereas maximal mononuclear cell accumulation was observed at 24 h after TEL injection. The same profile of neutrophil accumulation was observed when this lectin was injected into mouse peritoneal cavity, although the maximal mononuclear cell recruitment was observed 48 h after TEL injection. Additionally, TEL (12.5-200 microg/paw) caused a dose-dependent mice paw, as evaluated at 4 h after the lectin injection. D-mannose, better than D-glucose, significantly inhibited TEL-induced neutrophil migration into the peritoneal cavity or air-pouch. D-galactose had no effect on TEL-induced neutrophil migration in either cavity studied. On the other hand, D-mannose slightly inhibited the TEL-induced paw oedema, whereas neither D-glucose nor D-galactose affected this phenomenon. In conclusion, our data show that TEL induces neutrophil and mononuclear cell accumulation by a mechanism related to their specific sugar-binding properties.

Analysis of Variance↗

PubMed2002

Amisulpride for schizophrenia.

BACKGROUND: The treatment of schizophrenia with old, 'typical' antipsychotic drugs such as haloperidol can be problematic, because many people treated with these drugs will suffer from movement disorders. Amisulpride is said to be an "atypical" antipsychotic which induces less movement disorder and which is effective for the negative symptoms of schizophrenia. OBJECTIVES: To evaluate the effects of amisulpride as compared with placebo, typical and atypical antipsychotic drugs for schizophrenia. SEARCH STRATEGY: The authors carried out electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4, 1999), Cochrane Schizophrenia Group's Register (November 2000), EMBASE (1980-1999), LILACS(1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). They checked all identified studies for further trial citations, and sought these studies in the Science Citation Index. They also contacted authors of trials and the manufacturer of amisulpride. SELECTION CRITERIA: All randomised controlled trials comparing amisulpride to placebo, typical or atypical antipsychotic drugs for schizophrenia or other non-affective serious mental illnesses. DATA COLLECTION AND ANALYSIS: Data were independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated using a random effects model, and, where possible, the number needed to treat was calculated. Weighted mean differences (WMD) were calculated for continuous data. MAIN RESULTS: This review currently includes 19 randomised studies with a total of 2443 participants. Most trials were of short duration. Data from 4 trials with 514 participants with predominantly negative symptoms suggest that low-dose (up to 300mg/day) amisulpride was a more acceptable treatment than placebo (n=514, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 3 to 7), the improvement of the participants' global state (n=242, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 2 to 6) and the treatment of negative symptoms (n=177, WMD -10.1 CI -16.6 to -3.5). Amisulpride was shown to be more likely to cause extrapyramidal symptoms than placebo in two studies (n=269, RR 2.2 CI 1.2 to 4.2), but this result did not hold calculating the risk reduction so that an NNT-statistic could not be indicated. Compared to typical antipsychotics, the pooled results of a total of fourteen trials suggest that amisulpride was more effective in improving global state (n=651, RR 0.7 CI 0.5 to 0.9, NNT 6 CI 4 to 11), the general mental state (n=695, WMD -4.2 CI -6.5 to -1.9) and the negative symptoms of schizophrenia (n=506, WMD -2.8 CI -4.3 to -1.3). Regarding positive symptoms, amisulpride was as effective as typical antipsychotics. Amisulpride was less prone to cause at least one general adverse event (n=751, RR 0.9 CI 0.8 to 0.97, NNH 9 CI 6 to 18), one extrapyramidal symptom (n=771, RR 0.7 CI 0.6 to 0.9, NNH 5 CI 4 to 9) or to require the use of antiparkinson medication (n=851, RR 0.6 CI 0.5 to 0.8, NNH 4 CI 3 to 6). No clear differences in other adverse events compared to typical drugs were found. Amisulpride also seemed to be more acceptable than conventional drugs as measured by the outcome 'leaving the studies early' (n=1512, RR 0.8 CI 0.7 to 0.9, NNT 16 CI 9 to 69) than conventional drugs, but this result might have been overestimated due to a publication bias which could not be excluded with certainty. A single trial compared amisulpride to another 'atypical' antipsychotic, risperidone. With the exception of agitation, which was more frequent in the amisulpride group (n=228, RR 3.4 CI 1.2 to 10.1, NNH 11 CI 6 to 50) no significant differences were recorded on efficacy or acceptability. REVIEWER'S CONCLUSIONS: This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects. Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life.

Amisulpride↗

PubMed2001

Antidepressants for cocaine dependence.

BACKGROUND: Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. OBJECTIVES: To conduct a systematic review of all RCTs on the use of antidepressants for treating cocaine dependence. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Other searches:reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of antidepressants on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: 18 studies were included in the review, with 1177 people randomised. Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Antidepressive Agents↗

PubMed2001

Dopamine agonists for cocaine dependence.

BACKGROUND: Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. OBJECTIVES: To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. SEARCH STRATEGY: We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Twelve studies were included, with 587 participants randomised. Amantadine and Bromocriptine were compared to placebo in most of trials. In two studies amantadine was directly compared to bromocriptine, while amantadine was compared to desipramine, an antidepressant in three. The main efficacy outcome presented was positive urine sample for cocaine metabolites, with no significant differences between interventions. When retention in treatment was assessed as an acceptability measure, it was found a similar rate of patients remaining in treatment in both placebo and active drugs. There were no significant differences in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Amantadine↗

PubMed2000

A comparison of drugs versus placebo for the treatment of dysthymia.

OBJECTIVES: Dysthymia is a depressive disorder of chronic nature but of less severity than major depression, which depressive symptoms are more or less continuous for at least two years. The aim of this review was to conduct a systematic review of all RCTs comparing drugs and placebo for dysthymia. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from the pharmaceutical industry; book chapters on the treatment of depression. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of drugs versus placebo for dysthymic patients. Exclusion criteria were: non randomised, mixed major depression/ dysthymia (trials not providing separate data) and depression secondary to other disorders (e.g. substance abuse). DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently. In order to achieve an intention-to-treat analysis, when trials failed to report it was assumed that people who died or dropped out had no improvement. Authors of relevant trials were contacted for additional and missing data. Absence of treatment response as defined by authors was the main measure of outcome used. Relative Risks (RR) and 95% confidence intervals (CI) of dichotomous data were calculated with the Random Effects Model. Where possible, number needed to treat (NNT) and number needed to harm (NNH) were estimated, taking the reciprocal of the absolute risk reduction. MAIN RESULTS: Currently the review includes 15 trials. Similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for absence of treatment response was 0. 68 (95% CI 0.59-0.78) for TCA and the NNT was 4.3 (95% CI 3.2-6.5). SSRIs showed similar RR for this outcome: 0.64 (95% CI 0.55-0.74), the NNT being 4.7 (95% CI 3.5-6.9). Concerning MAOIs, the RR was 0. 59 (95% CI 0.48-0.71) and the NNT was 2.9 (95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results in terms of absence of treatment response. Using more stringent criteria for improvement - full remission - the results were unchanged. Patients treated on TCA were more likely to report adverse events, compared with placebo. REVIEWER'S CONCLUSIONS: Drugs are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or long-term outcome.

Antidepressive Agents↗

PubMed2000

Carbamazepine for cocaine dependence.

BACKGROUND: Cocaine dependence has become a substantial public health problem, developing a significant number of medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorder, has also been used for treatment of cocaine dependence, although its effectiveness has not been established. OBJECTIVES: To determine whether carbamazapine (CBZ) is effective on the treatment of cocaine dependence. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of carbamazepine drugs versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. MAIN RESULTS: 5 studies were included in the review, with 455 people randomised. No differences were found regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety Inventory slightly favoured carbamazepine, but didn't reach statistical significance. Dropouts were high in both groups up to 70% in the placebo group. Less dropout occurred in the Carbamazepine group (RR 0.87 95%CI 0.71-1.06). When no retention in treatment was due to side effects no differences were found. The number of participants presenting at least one side effect, reported in Kranzler (1995), was higher in the carbamazepine group (RR 4.33 95% CI 1.45-12.91). REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of CBZ in the treatment of cocaine dependence. Larger randomised investigation must be considered taking into account that these time-consuming efforts should be reserved for medications showing more relevant and promising evidence.

Anticonvulsants↗

PubMed2000

Combination of antidepressants and psychological treatments for bulimia nervosa: a systematic review.

UNLABELLED: This review assessed the effect of a combination of antidepressants plus psychological approaches compared to each single treatment for bulimia nervosa. METHOD: Trials were included in two meta-analyses: single antidepressants versus combination and single psychological approaches versus combination. Methodological quality and homogeneity of results were assessed. Dichotomous outcomes were analysed by calculating relative risks (RR). RESULT: Five trials were included in meta-analysis 1 and 7 in meta-analysis 2. Remission rates were 42% for combination versus 23% for antidepressants (RR = 1.38; 95% CI=0.98-1.93; P=0.06) and 36% for psychological approaches compared to 49% for combination (RR= 1.21; P=0.03). Drop-out rates were 16% for psychological approaches and 30% for combination (RR =0.57; 95% CI = 0.38-0.088; P=0.11). CONCLUSION: Efficacy of combined treatments was superior to single approaches. When antidepressants were combined to treatment, acceptability of psychological approaches was significantly reduced.

Adult↗

PubMed1999

Antidepressants versus psychotherapy for bulimia nervosa: a systematic review.

OBJECTIVE: To assess the efficacy and acceptability of antidepressants compared to psychotherapy as single approaches for the treatment of bulimia nervosa. METHOD: Dichotomous outcomes were analysed by calculating relative risks and continuous outcomes by calculating effect sizes. The number needed to treat (or harm) was calculated. Methodological quality of trials and heterogeneity in the results were evaluated. RESULTS: A meta-analysis including five randomized controlled trials showed a non-significant difference in short-term remission of bulimic symptoms favouring psychotherapy. Remission rates were 20% for antidepressants and 39% for psychotherapy (P = 0.07). Dropout rates were higher (P = 0.027) for antidepressants (40%) than for psychotherapy (18%). The number needed to harm (NNH) was 4. DISCUSSION: Psychotherapy was superior to antidepressants, but using a more conservative statistical approach this difference, although clinically relevant, was not significant. The number of trials might be insufficient to show the significance of a 20% absolute risk reduction in efficacy. Psychotherapy was a better accepted treatment.

Adult↗

PubMed1996

The effect of bile acid on the activation of amiloride-sensitive sodium channels in frog skin.

The effect of the bile acid, deoxycholic acid (DOC), on the transport properties of isolated frog skin was studied under short-circuit conditions. The addition of DOC (1 mM) to the apical side of the frog skin induced a threefold increase in the short-circuit current (Iac). This effect was inhibited by amiloride. DOC also increased the conductance of the preparation by two different mechanisms. At low concentrations (< 2.5 mM) it activated amiloride-sensitive sodium channels. At higher concentrations of DOC, basolateral-apical unindirectional fluxes, measured with 22Na+, 36Cl-. [14C]mannitol and [14C]inulin, showed a selective increase in the permeability to Na+, Cl- and mannitol in relation to [14C]inulin. These data suggest that sodium and chloride ions use the same diffusional pathway across the preparation. This pathway discriminates between NaCl and mannitol, and discriminates even more in relation to inulin. The effects of DOC are additive to those of cAMP (1 mM). ADH (20 mU ml-1), prostaglandin E2 (0.1 microM) or forskolin (10 microM). It is concluded from our study that the final effect of DOC in stimulating the Isc in frog skin is through the activation of amiloride-sensitive sodium channels. However, since DOC is liposoluble, a direct activation of an adenylate cyclase or of phosphokinase A cannot be excluded.

Amiloride↗

PubMed1996

Stressful life events and minor psychiatric disorders: an estimate of the population attributable fraction in a Brazilian community-based study.

OBJECTIVE: A population-based survey was conducted in Pelotas, southern Brazil, to assess the specific and the combined contribution of life events and socioeconomic factors on the overall prevalence of minor psychiatric disorders (MPD). METHODS: The study covered a representative sample of the population aged fifteen years or older living in the urban area of the city. Using multi-stage sampling, a total of thirty census tracts and 600 households were selected. A standardized questionnaire assessed the presence of MPD (using the Self-Reporting Questionnaire-SRQ-20), the occurrence of life events (death of a relative, a relative with a chronic disease, loss of employment, divorce, migration, accident, and robbery/assault), and socioeconomic factors. RESULTS: The prevalence of MPD was 22.7 percent (17.9% males and 26.5% females) and increased with age. Significant linear relationships with education and income were observed: the less education and income, the higher the prevalence of MPD. All life events, except migration and accident, were positively associated with MPD. People who experienced divorce in the last year had a prevalence of MPD three times higher than those who had not. The likelihood of MPD increased linearly with the number of life events. The highest proportion of Population Attributable Fraction for any life events was 24 percent. CONCLUSIONS: These data suggest that life events can explain a substantial proportion of MPD and with socioeconomic factors may be related to the onset of MPD.

Adolescent↗

PubMed1993

Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation.

The objective of this study was to evaluate the effects of a long-term, low-calcium diet on fetal calcium metabolism and fetal skeleton development in ewes. Eleven pregnant sheep were assigned to two groups, fed either a diet low in calcium (0.26% total dry matter) or normal in calcium (0.8% total dry matter) for 2 months, starting at 60 days gestational age. The ewes fed the low calcium diet showed lower plasma levels of calcium and higher plasma levels of hydroxyproline, parathyroid hormone, and 1,25(OH)2D compared with the ewes fed the normal calcium diet. There were no differences in these variables between the two groups of fetuses. These observations suggest that the plasma components of calcium homeostasis measured in the fetal lamb in the present study are independent of the ewe and are not significantly affected by the presence of lowered maternal calcium for many weeks during pregnancy. Despite the ability of the fetus of the ewe on the low calcium diet to maintain relatively normal circulating plasma components of calcium homeostasis, long-term maternal hypocalcemia delayed fetal skeletal ossification as shown by histological examination of the fetal humerus. The fetal humerus from low calcium-fed ewes showed a lower proportion of bone versus cartilage (45.6 +/- 5.9 versus 57.4 +/- 4.6%, mean +/- SD) lower ash content (15.4 +/- 1.5 versus 17.4 +/- 1.0%), and lower specific gravity (1.19 +/- 0.2 versus 1.22 +/- 0.02) (P < 0.05) than the humerus from fetuses of normal calcium-fed ewes. This study shows that the long-term calcium intake of the ewe does affect fetal skeletal development, despite a lack of observable effects on fetal plasma concentrations of calcium or known calcium regulating hormones such as 1,25(OH)2D or parathyroid hormone.

Animals↗

PubMed1990

Vaccination of humans against cutaneous leishmaniasis: cellular and humoral immune responses.

Brazilian army conscripts were vaccinated against American cutaneous leishmaniasis by using nonliving polyvalent promastigote Leish vaccine 5 or Leish vaccine 6 (vaccines with five or six Leishmania stocks) with or without Corynebacterium parvum. No statistically significant differences in lymphocyte stimulation indices were found between vaccinated groups with or without C. parvum, but lymphocyte stimulation indices of all vaccinees were significantly higher (P less than 0.001) than those of the placebo group. A correlation of 90% was found between positive skin test results and positive lymphocyte stimulation indices. Eight major antigens with estimated molecular masses of 13.5, 25, 40, 63, 73, 85, 97, and 160 kilodaltons were recognized by Leish vaccine 5 sera. Our finding also demonstrated the predominance of immunoglobulin M antibody in sera of vaccinated subjects and that a component of Leish vaccine 5, gp63, was immunogenic in humans both at the T-cell level and at the antibody level.

Adjuvants, Immunologic↗

PubMed1989

Immune responses during human schistosomiasis mansoni. XVI. Idiotypic differences in antibody preparations from patients with different clinical forms of infection.

Antibodies were purified from pooled sera from patients with different clinical forms of schistosomiasis mansoni on immunoaffinity columns of schistosome soluble egg Ag (SEA). As previously reported, T lymphocytes in PBMC preparations from schistosomiasis patients (but not control subjects who have never been infected) proliferate when cultured in the presence of certain of these anti-SEA purified antibodies. We now show that PBMC from most patients with chronic schistosomiasis, regardless of the clinical form of their infection, respond to anti-SEA antibodies from sera of asymptomatic (intestinal) or hepatointestinal patients. In stark contrast, none responds to anti-SEA antibodies purified from sera of acute or hepatosplenic patients. All of these multiclonal anti-SEA antibody preparations were active in anti-SEA ELISA assays and gave comparable patterns of reactivity with SEA upon immunoblotting analysis. Immunization of rabbits with some of these anti-SEA antibody preparations, followed by absorption of the rabbit antisera on absorbents of normal Ig, produced specific anti-Id reagents. Use of these reagents in competitive ELISA systems demonstrated that the Id in stimulatory and nonstimulatory anti-SEA antibody preparations differ with regard to the proportion of the serologically defined Id expressed by each. It appears possible to screen patients' plasmas for the presence of shared Id by use of suitable Id/anti-Id competitive ELISA assays. Taken together these data indicate that only certain Id-positive preparations are stimulatory to patients' PBMC, and the expression of these T cell stimulatory, immunoregulatory Id on anti-SEA antibodies correlates with the clinical form of a patient's infection.

Acute Disease↗