Polash Shajahan

Who responds to aripiprazole in clinical practice? An observational study of combination versus monotherapy:

We aimed to study aripiprazole, as monotherapy and combined with other antipsychotics, in routine clinical practice, to identify patients who had a favourable clinical response. We retrospectively identified all secondary care psychiatric patient records started on aripiprazole (n = 85). We assigned Clinical Global Impression scores to measure effectiveness. We examined demographic and clinical correlates of patients who improved (CGI Improvement scores < 5) versus those who did not improve (CGI ≥ 5). 56 patients (66%) received aripiprazole as monotherapy, 29 patients (34%) in combination with other antipsychotics. 52 patients (62%) received a CGI 1-4 (minimally to very much improved), 32 patients (38%) a CGI ≥ 5 (no change to very much worse). Patients who improved were less likely to have had previous or subsequent treatment with clozapine (p = 0.04). Discontinuation was due to agitation (35%), inefficacy (21%), nausea (18%) and worsening psychosis (12%). Combination with other antipsychotics resulted in less discontinuation and a lower maximum dose of aripiprazole. Aripiprazole was combined with other regular additional antipsychotics in 1/3rd of patients. Combination and monotherapy were clinically effective in around 60% of patients. Favourable response was associated with lack of treatment resistance. Agitation was the commonest reason for discontinuation.

Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate.

Objectives: In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. Method: The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan–Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Conclusions: Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time.

Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early discontinuation. APP had no adverse outcomes on assigned CGI improvement or mean end-point severity ratings for RLAI and zuclopenthixol decanoate.

Long-term antidepressant treatment in general practice: changes in body mass index

Aims and method To discern changes in body mass index (BMI) in patients on long-term antidepressant treatment in a general practice population and establish BMI changes in patients with and without a diagnosis of diabetes. We used a retrospective observational method and identified patients on four antidepressants of interest. We excluded those who did not have start and current BMI readings within the past 3 years and noted whether or not patients had a diagnosis of diabetes. Results Long-term treatment with citalopram, fluoxetine, mirtazapine and sertraline was associated with increased BMI in two-thirds of patients. There was reduction in BMI in patients with diabetes and an increase in BMI for patients who did not have diabetes. Clinical implications Awareness of environmental factors and their impact on individuals is important. Medication is not the only cause of abnormal metabolic effects. Overall monitoring of physical health is important in all groups of patients.

pharmacotherapy Update: Quetiapine use in Bipolar Disorder—What does the evidence tell us?

Bipolar disorder is a common and serious illness usually requiring long term medication. We critically review the available evidence surrounding the increasing use of quetiapine, a second generation antipsychotic, in both the acute and maintenance phases of bipolar disorder. Large scale, randomized controlled data supports the use of quetiapine in both acute mania and acute bipolar depression, as a safe and effective treatment and probably best used in combination with a traditional ‘mood stabiliser’ such as lithium or divalproex. Also, quetiapine monotherapy has been shown to be effective in bipolar depression. Two recently published studies also confirm that quetiapine in combination with either lithium or divalproex ‘adds value’ to the maintenance treatment of bipolar disorder in terms of delaying relapse compared to either lithium or divalproex alone. Quetiapine is generally well tolerated, although further work on long term weight gain and emergent diabetes would be helpful.