H Temmingh and DJ Stein,
CNS drugs, 2015
Anxiety symptoms can occur in up to 65 % of patients with schizophrenia, and may reach the threshold for diagnosis of various comorbid anxiety disorders, including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). We review the clinical presentation, diagnosis, neurobiology, and management of anxiety in patients with schizophrenia, with a particular focus on pharmacotherapy. The prevalence of any anxiety disorder (at syndrome level) in schizophrenia is estimated to be up to 38 %, with social anxiety disorder (SAD) being the most prevalent. Severity of positive symptoms may correlate with severity of anxiety symptoms, but anxiety can occur independently of psychotic symptoms. While anxiety may be associated with greater levels of insight, it is also associated with increased depression, suicidality, medical service utilization, and cognitive impairment. Patients with anxiety symptoms are more likely to have other internalizing symptoms as opposed to externalizing symptoms. Diagnosis of anxiety in schizophrenia may be challenging, with positive symptoms obscuring anxiety, lower levels of emotional expressivity and communication impeding diagnosis, and conflation with akathisia. Higher diagnostic yield may be achieved by assessment following the resolution of the acute phase of psychosis as well as by the use of screening questions and disorder-specific self-report instruments. In schizophrenia patients with anxiety, there is evidence of underactive fear circuitry during anxiety-provoking stimuli but increased autonomic responsivity and increased responsiveness to neutral stimuli. Recent findings implicate the serotonin transporter (SERT) genes, brain-derived neurotropic factor (BDNF) genes, and the serotonin 1a (5HT1a) receptor, but are preliminary and in need of replication. There are few randomized controlled trials (RCTs) of psychotherapy for anxiety symptoms or disorders in schizophrenia. For pharmacotherapy, data from a few randomized and open trials have shown that aripiprazole and risperidone may be efficacious for obsessive-compulsive and social anxiety symptoms, and quetiapine and olanzapine for generalized anxiety. Older agents such as trifluoperazine may also reduce comorbid anxiety symptoms. Alternative options include selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics, although evidence is based on a few randomized trials, small open trials, and case series, and caution is needed with regards to cytochrome P450 interactions and QTc interval prolongation. Buspirone and pregabalin augmentation may also be considered. Diagnosis and treatment of anxiety symptoms and disorders in schizophrenia is an important and often neglected aspect of the management of schizophrenia.