Obdulia Martínez-García

Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: Findings of a randomized clinical trial in a drug-naïve population

BACKGROUND There is little information about weight gain induced by antipsychotics at long-term. OBJECTIVE To quantify the weight gain induced by first (haloperidol) and second generation antipsychotics (olanzapine and risperidone) in a cohort of drug-naïve subjects after 1 year of treatment. METHODS This is a prospective, randomized clinical trial, including a representative sample of first episode psychotic incident cases from a population area of 555.000 people. The main outcome measures were changes in body weight and body mass index at 3 months and at 12 months. Both a per protocol analysis and an intention to treat analysis were conducted. RESULTS A total of 164 drug-naïve patients were included. At 12 months 144 patients were evaluated. Of them, 66% completed the protocol and 34% needed treatment switch. We found statistically significant differences in weight gain at 3 months: 3.8 kg (+/-4.1) for haloperidol, 5.9 kg (+/-5.1) for risperidone and 8.4 kg (+/-5.0) for olanzapine (F=7.045; p=0.002). After 1 year the difference in weight gain had disappeared: 9.7 kg (+/-5.7) for haloperidol, 8.9 kg (+/-8.8) for risperidone and 10.9 kg (+/-7.2) for olanzapine (F=0.817; p=0.445). CONCLUSIONS Drug-naïve patients experience an extraordinary weight gain after 1 year of treatment with haloperidol, olanzapine or risperidone. The main difference among these treatments is the pattern of weight gain but not the final amount of weight gain.

Epidemiological factors associated with treated incidence of first‐episode non‐affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis

Aim: The aim of the study was to analyse the treated incidence of schizophrenia in Cantabria (Northern Spain) and the sociodemographic risk factors associated with the illness onset.

Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naive population

OBJECTIVE This study examined the main metabolic side effects induced by antipsychotic treatment in a cohort of first episode drug-naïve subjects after the first year of treatment. METHODS A randomized, open-label, prospective clinical trial was conducted. Participants were 164 consecutive subjects included in a first episode program and never treated with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone. The main outcome measures were changes at 1 year in fasting glucose parameters (glucose, insulin levels and insulin resistance index) and changes in fasting lipid parameters (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol). RESULTS 144 of the total sample were evaluated at 1 year. There was a statistically significant increase in the mean values of insulin levels, insulin resistance index, total cholesterol, LDL-cholesterol and triglycerides. No pathological values in fasting glucose plasma levels were found at baseline and there were no changes after 1 year. Weight gain was positively correlated with changes in insulin levels, insulin resistance index and triglyceride levels. We did not detect statistically significant differences between treatments in any of the parameters evaluated. CONCLUSIONS Fasting glycaemia and insulin concentrations at baseline do not support the hypothesis that schizophrenia is associated with an underlying abnormality in glucose metabolism. The changes in insulin and lipid parameters at 1 year seem to be related to the magnitude of weight gain. There were no significant differences between haloperidol, olanzapine and risperidone concerning metabolic adverse effects after the first year of treatment.

Neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode psychosis: a randomized, controlled 1-year follow-up comparison.

OBJECTIVE To investigate the neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders. METHOD This prospective, randomized, open-label study was conducted from February 2001 to February 2005. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred four patients randomly assigned to haloperidol (N = 35), olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive evaluations at baseline, 6 months, and 1 year were included in the final analysis. Thirty-seven healthy individuals were also longitudinally assessed. A neuropsychological battery that comprised 9 cognitive domains was used. The contribution of clinical changes, concomitant medications, and the severity of motor side effects to cognitive changes was controlled. The main outcome measure was cognitive changes at 1-year follow-up. RESULTS The 3 treatment groups showed a significant improvement in cognitive scores after 1 year. The differential cognitive effectiveness between antipsychotics was insignificant. The magnitude of cognitive changes was similar in the 3 treatment groups and controls, although a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey Complex Figure Test was found in the treatment groups. Clinical changes, use of concomitant medications, and the emergence of motor side effects did not significantly account for cognitive changes over time. CONCLUSION Haloperidol, olanzapine, and risperidone were equally effective in treating cognitive deficits of psychosis. The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics. Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implications for developing novel approaches for cognitive pharmacotherapy in schizophrenia.

Prevention of antipsychotic-induced weight gain with early behavioural intervention in first-episode psychosis: 2-year results of a randomized controlled trial

While weight-management interventions are effective in attenuating antipsychotic-induced weight, there is no available evidence on their long-term effectiveness. This study sought to investigate the 2-year effects of an early behavioural intervention (EBI) designed to prevent antipsychotic-induced weight gain in first-episode psychosis (FEP) patients. Sixty-one FEP patients were randomized to receive either EBI or treatment-as-usual. Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion (3-month follow-up) with treatment effects maintained over 3months. Differences between groups were no longer significant by 12months. Weight-management interventions may need to be offered for longer periods to maintain preventative effects. Alternatively, booster sessions may need to be regularly delivered after intervention completion.

Cannabis abuse is associated with decision-making impairment among first-episode patients with schizophrenia-spectrum psychosis

BACKGROUND Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders. METHOD One hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset. RESULTS No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers. CONCLUSIONS Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?

Prognostic value of cognitive functioning for global functional recovery in first-episode schizophrenia

BACKGROUND It has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables. METHOD A total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method. RESULTS Sustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery. CONCLUSIONS The limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.

Effects of family psychoeducation on expressed emotion and burden of care in first-episode psychosis: a prospective observational study.

The present study aimed to examine the levels and interactions of family burden (FB) and expressed emotion (EE) in first episode psychosis (FEP) patients and, secondly, to observe the potential change after a brief psychoeducational group intervention implemented in a real world clinical setting. Twenty-three key relatives of FEP patients received a brief psychoeducational group intervention. FB and EE were assessed before and after the intervention. EE-change and correlations between variables were examined. Half of the sample of key-relatives showed high levels of EE. No severe family burden was observed. FB and EE did not change after the intervention. Family subjective and objective burden were correlated with emotional overinvolvement, but not with criticism. Brief psychoeducational groups may not be sufficient to reduce FB and EE associated to the experience of caregiving for a family member with a first-episode psychotic disorder.

Homocysteine and cognition in first-episode psychosis patients

In the last years, there has been growing evidence linking elevated homocysteine levels with cognitive dysfunction in several neurological and neuropsychiatric diseases. The aim of the present study was to investigate the potential relationship between elevated homocysteine levels and cognitive deficits in first-episode psychosis patients. Plasma levels and cognitive performance of 139 patients and 99 healthy volunteers were compared. Patients were classified as elevated homocysteine (>90 percentile for controls) and normal and compared on 22 cognitive outcome measures grouped into cognitive domains known to be impaired in schizophrenia. Patients had a statistically significant increase in plasmatic homocysteine levels. In addition, they presented with significantly increased cognitive deficits. However, no relationship between homocysteine levels and cognitive impairment was detected. These results suggest the need for further studies to clarify the role of homocysteine in the etiology and prognosis of psychosis.

First-episode schizophrenia patients neuropsychologically within the normal limits: Evidence of deterioration in speed of processing

In apparent contradiction to the notion of cognitive impairment as a core feature of schizophrenia, some studies have described a subgroup of patients neuropsychologically within normal limits. It remains to be determined whether this subgroup has intact cognitive functioning or a higher premorbid functioning that attenuates the evidence of deterioration. Out of a total of 111 patients with FES or schizophreniform disorder, 25 (23%) were classified as cognitive normal (CN) according to criteria based on performance in six basic cognitive dimensions and an overall composite score, and their cognitive profile was compared with that of 28 controls. The CN subgroup had better social premorbid adjustment and had a higher premorbid IQ than the cognitive impaired subgroup. There were no differences in the other pretreatment variables examined. The CN subgroup performed similarly to controls in the cognitive dimensions, including sustained attention, verbal memory and executive functions. These profiles remained mostly unaltered after controlling for premorbid IQ. The cognitive deterioration index, calculated by ratio of performance in general knowledge and vocabulary abilities to a measure of processing speed , showed that both patient subgroups had similar levels of deterioration and that this was significantly different to that of controls. Although FES patients performed within normal limits and better than cognitive impaired patients in a processing speed task, they did nevertheless display a pattern of deterioration in processing speed (in relation to their premorbid IQ) equivalent to that of those with marked impairments.