Abstract
Bipolar disorders are increasingly described in psychiatric practice. The well-known efficacy of these agents has led to growing interest in the potential value of newer anticonvulsants to treat bipolar disorders. Lamotrigine, an established anticonvulsant approved for the treatment of epilepsy, is recently being researched for use in bipolar I disorder. More recently, two large studies that were prospectively designed for pooled analysis compared lamotrigine with lithium and placebo in the maintenance treatment of patients with bipolar I disorder [1, 2]. Based on these, we decided to evaluate our experiences in a group of Turkish patients, retrospectively. To the best of our knowledge, this is the first study on lamotrigine in the treatment of affective disorders in Turkish patients.
Turkish patients fulfilling DSM-IV criteria, 17 for bipolar disorders (12 were bipolar I, and five bipolar II) were enrolled for the retrospective chart review [3]. Five patients also had psychiatric comorbidity (four had generalized anxiety disorder and the other one obsessive compulsive disorder). Sixteen patients were in a depressive, and the other one in a mixed episode. In all cases, lamotrigine was added to stable medication regimens which were only partially effective in ameliorating symptoms. Exclusion criteria were psychotic symptoms, discontinuing lamotrigine less than 6 weeks and severe physical illness. The Ethics and Research Board of the Hospital approved the protocol. Lamotrigine had been initially added to existing mood stabilizing treatments at a starting dose of 25–50 mg day−1. Doses had been typically increased whenever possible by 50–100 mg day−1 every 2 or 3 weeks, and in some cases reached up to 400 mg day−1 according to the clinical response or optimal tolerability. Only one patient had taken a possible interacting drug (valproic acid 1000 mg day−1) with lamotrigine and about the others' co-medications, there had not been any evidence of interaction. During treatment, the patients were followed-up by the same psychiatrists for 2–4 weekly intervals and the therapeutic response was assessed via Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI). This retrospective chart review was based upon the initial, 2nd (3–4 weeks) and 3rd (6–7 weeks) follow-up measurements. Response to lamotrigine was defined as at least 50% reduction in HDRS (depressed patients) scores from baseline.
For statistical interventions SPSS (Statistical Package for Social Sciences Inc., Chicago, IL, US) for Windows 10.0 program was used. The result was accepted as significant when p = 0.05.
Table 1 shows some sociodemographic and clinical features of the study. It was seen that the patients continued to have co-medications such as antidepresants, benzodiazepines, mood stabilizers and antipsychotics. Thirteen patients responded to therapy. There was a significant difference between baseline, 2nd and 3rd HDRS scores (p ≤ 0.01) and CGI (p ≤ 0.01). Therefore, overall response rate was 76%. Of the five bipolar depressives, one of whom was comorbid with anxiety and one with mixed state, did not respond. Although two bipolar depressives switched to manic episodes according to the DSM-IV criteria under lamotrigine treatment, these were also included in the responder group (at least 50% reduction in HDRS scores). Lamotrigine was generally well tolerated. Cholestatic jaundice and polyuria were observed in two patients, thus lamotrigine was discontinued although patients were responding [4]. However, no other serious side effects had been reported such as serious rash or Stevens Johnson's syndrome.
Baseline sociodemographic and clinical characteristics of the sample population
CGI, Clinical Global Impression; HDRS, Hamilton Depression Rating Scale; SD, Standard Deviation.
This retrospective chart review suggests that adjunctive lamotrigine may be an effective and well-tolerated treatment for bipolar and unipolar depression. The significant improvement has been observed from the 4th week both in HDRS scores and CGI (p ≤ 0.01). These findings are consistent with other preliminary reports suggesting that lamotrigine may have both moodstabilizing and antidepressant properties in patients with bipolar disorder. Recently Montes et al. reported similar efficacy of lamotrigine in 34 patients and also long-term remission [5]. However, two bipolar patients switched to manic state, thus its putative role as a mood-stabilizing agent still remains unclear. The retrospective design, absence of a control group, small sample size and concomitant use of other medications are very important limitations. Also, given the recurrent nature of bipolar disorder, spontaneous improvement and remission cannot be excluded. However, these patients were with extensive past medication treatment and limited treatment response. Since lamotrigine was predominantly administered as add-on therapy, it is not possible to evaluate its independent action. However, it was encouraging that the response was observed in 76.5% of patients. The results of our report suggest that the drug should be investigated in long-term stabilization.
Although this study had few patients, lamotrigine was shown to be effective on bipolar depressive episodes in most but not all cases. Fewer side effects were observed but as in the apparent jaundice case, clinicians should be aware of unwanted effects during application of the drug.
Nevertheless, this is the first retrospective chart review to assess the efficacy and safety of lamotrigine in Turkish patients and it found 76.5% remission rates with fewer side effects. Controlled trials are now needed to confirm the mood-stabilizing effects of lamotrigine.