The pattern of pharmacological treatment of bipolar patients discharged from psychiatric units in Poland

Abstract

Background

The concomitant use of two or more mood stabilisers (MS), second-generation antipsychotics (SGA), lamotrigine as well as antidepressants, is frequently reported in the treatment of bipolar patients The aim of this study was to investigate the pattern of pharmacological treatment with special regard to polypharmacy defined as two or more psychiatric drugs taken at the same time in the same patients with bipolar disorder discharged from psychiatric units in Poland.

Method

Pharmacotherapy of 127 consecutive patients (57 females and 70 males) with an ICD-10 diagnosis of bipolar disorder (BP) at the point of discharge from five psychiatric regional hospitals/units in Poland, was evaluated in 2015/2016 on the basis of medical files. The effect of treatment on mental status at discharge was examined using the Clinical Global Impression-Improvement scale (CGI-I).

Results

When only MS, SGA and lamotrigine, were taken into account, 78 (61%) of patients were prescribed two, 27 (21.3%) three and one patient four medications. The combination of MS and SGA was most commonly used (n = 61, 48%). Medications preferred by Polish psychiatrists at patients’ discharge were valproates (n = 69, 54%), olanzapine (n = 48, 37%), quetiapine (n = 47, 37%) and lamotrigine (n = 33, 25.9%). Thirty patients (23.6%) were prescribed lithium. No relationships were found between polypharmacy and patients’ age, duration of illness and the rate of CGI-I. However, polypharmacy was significantly associated with types of bipolar disorder, particularly with the bipolar I disorder.

Conclusion

The prevalence of polypharmacy especially with MS and SGA in the treatment of bipolar patients discharged from psychiatric units in Poland is high. The most significant factor predisposing to polypharmacy is a diagnosis of bipolar – I disorder. In general, our study confirms trends observed in other countries.

Introduction

Demonstrating mood-stabilizing properties of lithium [1], valproates [2] and carbamazepine [3] were milestones in the development of pharmacological management of bipolar disorder (BD). Because of the prophylactic effect of BD these drugs have been referred to as mood stabilisers (MS). The spectrum of pharmacological methods of treatment of BD has significantly increased at the end of the 20th century and the beginning of the 21st, when the efficiency of second-generation antipsychotics(SGA): aripiprazole, olanzapine, risperidone, quetiapine, asenapine and ziprasidone, as well new generation of antiepileptic drugs (lamotrigine) in the treatment of acute episodes of BD and their prevention has been established. Therefore, both SGA and lamotrigine are considered as the second generation of MS.

In 2007 three criteria have been proposed for medications to be admitted to this group: (a) efficacy in treating the acute episodes of mania, (b) efficacy in the treatment of bipolar depression as well as (c) prophylactic effect against future episodes [4]. The risk of relapse following acute episode is high in bipolar patients, therefore the selection of optimal prophylactic treatment is an important therapeutic decision. The prevailing opinion is that lithium is the closest to ideal MS [5]. For this reason, lithium is recommended as first-line monotherapy for the relapse prevention [6]. Unfortunately, lithium effectively prevents relapses only in one-third of patients who are called “excellent lithium responders” while in others the effect is not satisfactory [7]. Also, other medications seem to have a limited range of efficacy. Results of meta-analyses of randomised control trials with relapse prevention designs, which formed the basis for formulating therapeutic guidelines, revealed that olanzapine, quetiapine, risperidone (long-acting injection) and valproate are effective in the prevention of manic relapse while lamotrigine and quetiapine more effectively prevent depressive relapse [6].

The lack of “an ideal” MS encourages clinicians to consider augmentation of the ineffective or partially effective drug with the second medication. In clinical practice concomitant use of two or more drugs in the treatment of BD is common. For example, participants of the STEP-BD study, who achieved a remission of symptoms were prescribed averagely 2.05 medications [8]. Using a retrospective chart review of 230 BP patients admitted to hospital in 2010, Weinstock et al. [9] found that patients took an average of 3.31 (SD = 1.46) psychotropic medications at the time of hospitalization. Moreover, 55% of them reported taking 3 or more psychotropic medications and 36% reported taking ≥4 psychotropic medications. Data from a large European multicenter study (AMSP) showed that from 1994 to 2009, 85% of all BP patients received more than one class of psychotropic medications. Moreover, as many as 74% of patients received antidepressants, most commonly in combination therapy with lithium or valproates particularly in bipolar depression [10]. Italian Burden of Illness in Schizophrenia and BD (IBIS) study demonstrated that 69% of BP patients were treated with antipsychotics (AP) and 30.4% of them received AP polypharmacy. Moreover, 85.5% of those who were on AP polypharmacy received also mood stabiliser and/or antidepressant. In turn, 76.9% of bipolar patients who were on one AP, received concomitant treatment with MS and/or antidepressant [11]. In Taiwan, 71% of bipolar patients received two or more medications from different classes (MS + SGA). The most common combination was the concomitant use of mood stabiliser and SGA [12].

Several definitions of polypharmacy have been proposed by authors of studies published so far. One of them, commonly used says that this is the long-term use of two or more psychiatric medications in the same patient and the second that it refers to use of two or more medication of the same class to treat the same condition [13].

Treatment guidelines published in recent years recommend monotherapy, preferably with lithium, and augmentation with valproates or SGA if lithium is ineffective [6,[14], [15], [16], [17]]. In rapid cycling BD combination treatment is especially recommended [6,15]. Also, Polish standards of pharmacological treatment of BD recommend monotherapy as a first-line method of prophylaxis of recurrences [18].

The aim of this study was to assess the pattern of pharmacological treatment in patients with the diagnosis of BD discharged from psychiatric units in Poland. Furthermore, the study aimed to identify clinical and demographic factors predisposing to polypharmacy.