Carbamazepine as adjunctive treatment in nonepileptic chronic inpatients with EEG temporal lobe abnormalities. [Adjuvant treatment of schizophrenic illness with carbamazepine]. Carbamazepine as an adjunct of antipsychotic therapy. Carbamazepine maintenance treatment in outpatient schizophrenics. [Carbamazepine: an efficient adjuvant treatment in schizophrenia]. A double-blind trial of carbamazepine in negative symptom schizophrenia. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
A 15-week double-blind, randomized, within-patient design was used to assess carbamazepine versus placebo as adjunctive treatment in chronic hospitalized psychiatric inpatients (predominantly schizophrenic) with EEG temporal lobe abnormalities but no clinical evidence of epilepsy. A statistically significant improvement on carbamazepine was found on all clinical rating measures used (Overall Clinical Rating, Brief Psychiatric Rating Scale, and Global Assessment). The results also appeared to be clinically significant. Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy. The effect of low-dose haloperidol combined with the anticonvulsant carbamazepine was investigated in a 5-week placebo-controlled, double-blind study in acute schizophrenic patients. Weekly ratings showed a clinically pronounced and statistically significant improvement in both the carbamazepine and placebo groups. However, the patients on carbamazepine needed less neuroleptic and anticholinergic medication and experienced fewer side effects compared to the patients on placebo. Moreover, patients in the carbamazepine group showed a clear deterioration after discontinuation of carbamazepine (but maintenance of neuroleptic medication), while the placebo group did not change after discontinuation of placebo. Concomitant treatment with carbamazepine in psychotic patients may help to reduce neuroleptic dosages and unwanted side effects. A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena. Different studies published in the last years have focused on the psychotropic effects of carbamazepine (CBZ). This study tries to investigate the efficacity of CBZ as an adjunct treatment of schizophrenia. 20 patients with a diagnosis of paranoid schizophrenia, according to the RDC, have been investigated by double-blind method. Subjects are divided in two groups (n = 10). The first one is treated with CBZ (with dose in order to reach a plasma level between 8-12 mg /l) and Haloperidol (oral fixed dose: 30 mg /day). The second group only with Haloperidol (same dose). Clinic and psychopathological disturbances are evaluated with the BPRS, and secondary effects with the UKU scale. A clinical improvement (90%, measured by the BPRS) was observed for both groups, without significant differences. Patients treated with CBZ show an important reduction of neurological secondary effects related to neuroleptics (Haloperidol). Carbamazepine appears to be a useful treatment, combined with neuroleptics, for acute schizophrenic episodes. Twenty-eight residual schizophrenics hospitalized in a chronic institution with a 9 to 30 year history of disease, with predominantly negative symptoms were given carbamazepine. Carbamazepine was administered in a double-blind trial and therapeutic effects were measured by the Scale for the Assessment of Negative Symptoms (SANS). Patients were also assessed for positive symptoms using the Brief Psychiatric Rating Scale (BPRS), for depression using the Hamilton Depression Scale, for extrapyramidal symptoms by the Simpson and Angus scale, to rule out these symptoms as sources of secondary negative symptoms. The study continued for 7 weeks with therapeutic carbamazepine levels achieved during the last 5 weeks. There was no significant positive effect of carbamazepine on negative symptoms. Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.
                SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.
                For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.
                Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.
Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.