Anxiety is a core symptom of schizophrenia that elicits significant subjective burden of disease and contributes to treatment resistance in schizophrenia. Anxious syndromes might be attributed to incompletely remitted delusions, the negative syndrome, depressive episodes, panic attacks, social phobia, avoidance after hospitalization, and down-tapering of benzodiazepine medication. Pregabalin, an antagonist at the alpha2delta subunit of voltage-gated Ca channels, modulates several neurotransmitter systems and was found to alleviate anxiety in different mental disorders. In schizophrenia, this treatment option has not been evaluated before.Here, we report a case series of 11 schizophrenic patients who had treatment-resistant anxiety and received augmentation with pregabalin. This observational analysis reveals that the strategy was able to significantly reduce scores on the Hamilton anxiety scale; furthermore, we observed improvements of psychotic positive and negative symptoms and mood as assessed by Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and Calgary Depression Scale for Schizophrenia. After augmentation, both a complete discontinuation of concomitant benzodiazepine treatment as well as a dose reduction of antipsychotics could be achieved. We did not observe pharmacokinetic interactions or adverse events.These observations suggest that treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable. Further investigations should differentiate schizophrenic subsyndromes of anxiety and evaluate benefits and risks of pregabalin in comparison to placebo and active competitors.
Pregabalin was started with 75 mg/d and raised according to clinical necessity to a mean dose of 313.6 mg/d after a mean observation period of 6.7 weeks. Serum levels were assessed in a subgroup of 5 patients (mean dose, 375 mg/d; mean serum level, 1.7 mg/L). We observed improvements of anxiety (HAMA: P = 0.007, t16.9 = 3.041, effect size = 1.2) and mood (CDSS P = 0.002, t17.3 = 3.754, effect size = 1.6) (Fig. 1A). In addition, psychotic positive (PANSS positive: P = 0.009, t16.1 = 2.962, effect size = 1.3), negative (PANSS negative: P = 0.093, t17.7 = 1.773, effect size = 0.8; and SANS: P = 0.076, t19.1 = 1.875, effect size = 0.8), and global psychopathology (PANSS global psychopathology: P <= 0.000, t19.526 = 4.948, effect size = 2.1) responded, resulting in significantly decreased total PANSS scores (P <= 0.000, t16.6 = 4.326, effect size = 1.8) (Fig. 1B). In particular, partially remitted formerly treatment-resistant psychotic symptoms responded to the add-on of pregabalin.
I’d like to hear from anyone who has used pregabalin as an augmentation strategy in schizophrenia.