Pregabalin for anxiety in patients with schizophrenia — A randomized, double-blind placebo-controlled study
Introduction
Schizophrenia is a severe chronic mental disorder affecting approximately 0.5% of the population, with up to 10% of patients being institutionalized (Uggerby et al., 2011). Anxiety symptoms have been recognized as a core aspect of the psychopathology of schizophrenia (Kraepelin et al., 1919), but the diagnostic approach is inconsistent. Whether the anxiety symptoms in schizophrenia differ qualitatively from conventional anxiety disorders remains unclear (Bosanac and Castle, 2015), and the severity of anxiety may fluctuate with other symptoms throughout the course of the disease (Braga et al., 2013). Anxiety in schizophrenia is associated with increased risk of suicide, sleeping disturbances and reduced quality of life (Huppert et al., 2001). Benzodiazepines and antidepressants have been used to treat anxiety in patients with schizophrenia, although the evidence remain sparse (Braga et al., 2004). The use of benzodiazepines is controversial as these have been associated with increased mortality in patients with schizophrenia (Tiihonen et al., 2012). Pregabalin has been shown effective in generalized anxiety disorder (GAD) (Bech, 2007, Feltner et al., 2008) with efficacy comparable to lorazepam and venlafaxine, but with a more favorable cognitive profile than that seen with the benzodiazepines (Hindmarch et al., 2005). Pregabalin is not approved for the treatment of anxiety in schizophrenia, but it has been suggested that pregabalin may have a role as an “off label” add-on treatment for anxiety in schizophrenia (Englisch et al., 2010, Schonfeldt-Lecuona et al., 2009). As no randomized studies have been conducted so far, this study aimed to evaluate the efficacy and safety of pregabalin as add-on treatment for anxiety in patients with schizophrenia by using the Hamilton Anxiety Scale (HAM-A) as primary outcome.
Section snippets
Materials and methods
This investigator-initiated study was designed as a randomized, double-blind, placebo-controlled study. Patients were recruited from different psychiatric outpatient clinics or psychiatric departments in all five regions of Denmark. Patients were randomized 1:1 to either placebo or pregabalin as add-on treatment. First patient was included at 5th of March 2012 and last patient ended the study at 15th of August 2016. The study was ended before sample size goal was met due to failure in accessing
Participants flow
A CONSORT diagram of participants flow through the study is shown in Figure 1. Fifty-four patients were allocated to treatment and 46 patients (85%) completed the full study. At the assessment after 4 weeks of treatment the median daily dosage of pregabalin/placebo was 450 mg, ranging from 150 to 600 mg in both treatment groups. At the assessment after 8 weeks of treatment the median daily dosage of pregabalin/placebo was 600 mg in both groups, ranging from 450 mg to 600 mg in the placebo group and
Discussion
This is the first study to investigate the effects of pregabalin on anxiety in patients with schizophrenia. On the primary outcome, we found no statistical difference on the total HAM-A14. In the analyses of the subscales of the HAM-A, we found a clinically relevant difference between groups on the psychic factor of the HAM-A, whereas no difference was seen on the somatic factor. A clinically relevant difference between treatment groups on HAM-A6 was found, with a medium effect size. The HAM-A6
Contributors
JN designed the study and wrote the study protocol. JN and OS acquired the data and performed the statistical analyses. OS, PD, KDJ and JN interpreted the data and drafted the initial manuscript. All authors contributed in the final drafting and critically revised the manuscript.
Role of the funding source
This work was supported by an Investigator-Initiated Research (IIR) Award from Pfizer (Study ID# WS726958). Pfizer had no role in the study design, data collection, statistical analysis, interpretation, or writing of the manuscript. The corresponding author was responsible for the content of the manuscript and the decision to submit for publication. Additional funding was received from the Psychiatric Research Fund, Aalborg University Hospital, Denmark.
Conflicts of interest
OS has received speaker honoraria from Lundbeck Pharma. PD has received consultancy payment from Fertin Pharma. KDJ has been a consultant for AstraZeneca, on an advisory board for Bristol Myers Squibb and received speaker's honoraria from Lundbeck Pharma. JN has received speaker honoraria from Hemocue, Lundbeck, Sunovion and Bristol Myers Squibb and research grants from H. Lundbeck and Pfizer. SEL reports no financial relationships with commercial interests.
Acknowledgements
None.
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