Augmentation with pregabalin in schizophrenia

Augmentation with pregabalin in schizophrenia.

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.


panss pregabalin

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.

Pregabalin may also be effective in treating alcohol dependence [1] Rarely, pregabalin-associated elevation of clozapine serum levels have been reported [2, 3]

I’d like to hear from anyone who has used pregabalin as an augmentation strategy in schizophrenia.

2 thoughts on “Augmentation with pregabalin in schizophrenia

  1. I was pleased that my doctor was willing to prescribe some pregabalin. I’ve had a few changes to other medications (decreasing clozapine and increasing aripiprazole) but the anxiolytic (even somewhat pro-social and empathogenic) effects have been well received. I’m over the ‘intoxicating’ effects (albeit the first two days at 150mg were very productive, my level of goal-orientated activity sky rocketed) and stable at 150mg b.d. Worthy of mention is the profound suppression of alcohol cravings (I can finally say ‘no’ to alcohol without any desire to drink) and to a lesser degree, cravings for ‘novelty inducing’ supplements and the like. There hasn’t been much in the way of changes to the auditory hallucinations, perhaps even a slight worsening [potentially due to the other medication changes and a bit more stress], but the anxiolytic effect helps me in dealing with them. Unfortunately, I’m noting some greater cognitive impairments than normal, particularly with my memory, and I’m not sure it will be great for any coming efforts at returning to study. I’ll see how it goes.


  2. I’ve increased to 150mg pregabalin tds and the anxiolytic effects seem to be more stable and pronounced than with twice daily administration (with twice daily administration I had periods of feeling quite dissociated but that has been less prominent on the tds regime). There is slight disinhibition which is worthy of remaining vigilant for. Memory impairments seem comparable to the lower dose.

    The alcohol craving suppression is still effective and I’ve been able to remain abstinent.

    At 150mg b.d. there was a desire to augment with synergistic medications, or increase my dose. So far, at 150mg tds that hasn’t been a problem.

    I’ve also increased my aripiprazole to 30mg/day which is causing some agitation/akathisia – I partially attribute increases in nicotine gum use to attempts at self-medicating that.

    Auditory hallucinations have slightly attenuated in volume but not in terms of distressing content or frequency. I think the pregabalin does help with the associated anxiety.

    My attention span is still poor and my stream of thoughts very fragmented.

    I’ll be returning to study soon which will really test my social skills, cognition and stress management skills… I’ll post an update once I’ve had a go under those conditions.


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