I.B. Chaudhry

Minocycline benefits negative symptoms in early schizophrenia : a randomised double-blind placebo-controlled clinical trial in patients on standard treatment

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such ‘negative’ symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascuLar disease (CVD) and reduced Life expectancy, over and above that imposed by their mentaL illness through suicide. Several Levels of evidence from data Linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metaboLic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.

Prevalence and social correlates of postnatal depression in a low income country

SummaryBackground: Postnatal depression is an important public health problem worldwide. Recent evidence suggests that rates may be relatively higher in developing countries. We aimed to explore the prevalence of postnatal depression and its association with social support and other risk factors in a sample of Pakistani women. Methods: Population-based survey of 149 women at 12 weeks postnatal using the Edinburgh Postnatal Depression Scale (EPDS), Multidimensional Scale of Perceived Social Support (MSPSS) and Personal Information Questionnaire (PIQ). Results: Thirty six percent women scored ≥12 on EPDS. High depression score was associated with lower social support, increased stressful life events in the preceding year and higher levels of psychological distress in the antenatal period. Conclusions: There is a high prevalence of postnatal depression in Pakistani women. Early interventions should be developed that target the antenatal period and strengthen social support networks in women at risk.

The relationship between anxiety, depression and illness perception in tberculosis patients in Pakistan

ObjectiveAs the rates of TB world over have increased during the past 10 years, there has been a growing awareness of depression and its role in the outcome of chronic disorders. Though depression is common in patients with TB no study as yet has examined the prevalence of depression in this group in Pakistan. We aimed to determine the presence of depression, anxiety and illness perceptions in patients suffering from Tuberculosis (TB) in Pakistan.Methods108 consecutive outpatients with tuberculosis completed the Hospital Anxiety and Depression scale (HADS) and the Illness Perception Questionnaire (IPQ).ResultsOut of 108 patients, 50 (46.3%) were depressed and 51 (47.2%) had anxiety. Raised depression and anxiety scores were associated with an increase in the number of symptoms reported (HADS Depression: r = 0.346, p = < 0.001), more serious perceived consequences (HADS Depression: r = 0.279, p = 0.004, HADS Anxiety: r = 0.234, p = 0.017) and less control over their illness (HADS Depression: r = 0.239, p = 0.014, HADS Anxiety: r = 0.271, p = 0.005).ConclusionWe found that about a half of patients in our sample met the criteria for probable depression and anxiety based on HADS score. Negative illness perceptions were clearly related to reports of mood symptoms. As depression and lack of perceived control over illness in those suffering from tuberculosis are reported to be independent predictors of poor adherence further studies to investigate their relationship with medication adherence are required.

A population‐based study of irritable bowel syndrome in a non‐Western population

Abstract  Previous studies have found no female predominance in irritable bowel syndrome (IBS) in non‐Western countries. The aim of the study was to assess the prevalence and correlates of Rome II (IBS) in both sexes in Pakistan. A Population‐based survey in a low‐income inner city area using questionnaires to diagnose Rome II IBS and assess distress, disability and stressful life events. Data were collected from 880/938 (93%) randomly selected residents. 13.4% of women and 13.1% men met criteria for Rome II IBS; 34 (3.9%) had diarrhoea‐predominant, 59 (6.7%) had constipation‐predominant IBS and 24 (2.7%) had ‘mixed IBS’. In logistic regression analysis, IBS was associated in men with high income (OR = 1.56; 95% CI: 1.05–2.3) and few years of education (OR = 2.17; 95% CI: 1.2–3.9) and in women with being married (OR = 3.6; 95% CI: 1.1–11.9) and stressful life events score (OR = 1.14; 95% CI: 1.01–1.3). Disability was associated with constipation‐predominant IBS (OR = 1.99; 95% CI: 1.1–3.6), distress (OR = 1.19; 95% CI: 1.14–1.23) and stressful life events (OR = 1.19; 95% CI: 1.1–1.3). Investigations were more likely in men (54%) than in women (27%) (P = 0.003). These findings suggest that the equal sex ratio of IBS in urban Pakistan could result from a close association between marked distress and IBS in men similar to that found in women in western studies.

Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (≤ 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (≥ 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research.

Multidimensional scale of perceived social support : Psychometric properties in a South Asian population

Aim:  The Multidimensional Scale of Perceived Social Support (MSPSS) was developed to assess perceived social support, and has been widely used in Western samples. We attempted to translate and adapt this scale into the Urdu language, and herewith report on its psychometric properties in a rural Pakistani setting.

Impact of early intervention services on duration of untreated psychosis : data from the National EDEN prospective cohort study

OBJECTIVE This study aimed to determine if the inception of Early Intervention Services (EISs) is followed by an improvement in the prompt treatment of people with first episode psychosis. METHOD A prospective cohort study of referrals to new and established EISs was conducted at 1, 2, 3, and 4 years after inception of new EIS. The study was conducted with 14 (seven new and seven established) secondary care EIS within geographically defined catchment areas in England between 2005 and 2009. Participants included 1027 consecutive referrals to EIS aged 14-35 with a first episode of psychosis. Duration of untreated psychosis (DUP) and number of participants treated adequately within 6 months of onset were the main outcome measures. RESULTS A significant downward trend across yearly cohorts for DUP for new EIS (F1,549=8.4, p=0.004) but not for established EIS (F1,429=1.7, p=0.19) was observed. There was a significant upward trend across cohorts in the proportion of referrals treated within 6 months for new EIS (X(2)=8.0, df=1, p=0.005), but not for established EIS (X(2)=0.1, df=1, p=0.72). CONCLUSION The introduction of new EIS was followed by a reduction in DUP and an increase in the proportion of patients treated within 6 months of onset. These trends were not present in the catchment areas of established services where DUP was initially lower, suggesting that there was no general tendency for DUP to fall over time. Hence, the introduction of an EIS was followed by an improvement in the prompt and proper treatment of first episode psychosis.

Effects of the 5HT antagonist cyproheptadine on neuropsychological function in chronic schizophrenia

This study tests the hypothesis that the ability of atypical neuroleptics to improve negative symptoms is due to 5HT-receptor antagonism and enhanced frontal lobe function. We investigated the effects of cyproheptadine (a 5HT2 antagonist) on neuropsychological tests of frontal lobe functions in chronic schizophrenic patients. Eighteen stable schizophrenic patients on depot neuroleptic medication participated in a 4-week double blind crossover study. Outcome measures were clinical symptoms rating scales, neuropsychological tests (verbal fluency, Stroop colour word task, trail making) and antisaccade eye movements. During the cyproheptadine phase statistically significant improvement was seen on Stroop colour word task, verbal fluency and Trail B tests. The ability to suppress reflexive eye movement to a target light in an anti saccade task was also significantly enhanced. The patients had low clinical ratings of negative symptoms and they were unaffected by cyproheptadine. The results indicate that 5HT2C receptors selectively modulate speed and motor control mechanisms related to frontal lobe functions but this was not associated with changes in symptoms.

Brief psychological intervention after self-harm: randomised controlled trial from Pakistan

BACKGROUND Self-harm is a major risk factor for completed suicide. AIMS To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training (C-MAP) - delivered following an episode of self-harm compared with treatment as usual (TAU). METHOD The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation. RESULTS A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU. CONCLUSIONS The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention.