Changes in mood stabilizer prescription patterns in bipolar disorder

Highlights

• We studied prescription drug trends in bipolar disorder 2007–2013.

• Lithium prescription decreased in both bipolar disorder type I and II.

• The use of lamotrigine and quetiapine increased in both bipolar subtypes.

• Valproate use decreased in bipolar II disorder, and olanzapine use decreased in women.

• The prescription of antidepressants increased somewhat but only in bipolar I disorder.

Abstract

Background

Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007–2013.

Methods

Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipoläR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder.

Results

In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder.

Limitations

We only report data from 2007 as the coverage of BipoläR prior to 2007 was too low to allow for reliable analyses.

Conclusion

Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder.

Introduction

Bipolar disorder affects around 1.5% of the population (Altshuler et al., 2010) and entails high costs for the society, mainly due to long periods of sick leave (Ekman et al., 2013). The course of the disorder varies considerably between individuals. Some patients are free from affective recurrences for decades, while others frequently recurrent into severe manic or prolonged depressive episodes (Goodwin, 2007). While some persons recover completely between mood episodes, others suffer persisting, debilitating symptoms. The subdivision into bipolar disorder type I and II is established but not undisputed (Akiskal, 1996, Akiskal et al., 2000, Cassano et al., 1989, Cassano et al., 1992, Paris, 2009), and bipolar disorder type II does not exist as a diagnosis of its own in ICD-10.

In addition to treatment for acute depressive and manic episodes, there is effective prophylactic treatment available for bipolar disorder. It has been known for more than half a century that lithium effectively prevents new episodes (Geddes and Briess, 2007, Goodwin, 2002, Goodwin and Geddes, 2003), and lithium is still recommended as a first line maintenance treatment option according to national and international treatment guidelines (APA, A.P.A., 2002, Goodwin, 2009, NCCMH, 2006, SBU, 2004, Suppes et al., 2005, Yatham et al., 2013, Yatham et al., 2009). Lithium is known as a mood stabilizer. The definition of mood stabilizer is a treatment that is effective against either depression or mania without increasing the risk for an opposite episode. Some antipsychotic drugs are effective against mania, but may increase the risk of depression (Goikolea et al., 2013, Tohen et al., 2003, Zarate and Tohen, 2004). Contrariwise, antidepressant drugs may trigger mania when given as monotherapy to bipolar patients (Viktorin et al., 2014). In addition to lithium, several other drugs have now been proven effective not only for treatment of acute episodes but also for prophylaxis and are included among first line treatment options. Thus, besides lithium the mood stabilizer group comprises some antiepileptic drugs (valproate, carbamazepine, lamotrigine) and some atypical antipsychotic drugs (quetiapine, olanzapine, aripiprazole) (Coryell, 2009).

It has been suggested that the classic manic-depressive disorder with euphoric manias and full recovery between recurrences would respond particularly well to lithium (Dilsaver et al., 1993, Keller et al., 1993), while persons with mixed episodes and persons with rapid cycling would respond better to valproate (Bowden, 1995, Calabrese et al., 1996, Freeman et al., 1992, Swann et al., 1997). Olanzapine is prescribed mostly for mania but may also be used for acute bipolar depression in combination with fluoxetine (Taylor et al., 2014, Yatham et al., 2013). Lamotrigine is considered primarily to protect against depressive recurrences (Calabrese, 2004, Calabrese et al., 2003a, Calabrese et al., 2008, Calabrese et al., 2003b, Frye et al., 2000) and could therefore earn its place when preventing mania is less critical, as in bipolar disorder type II. Quetiapine is used for both depression and mania, but is also the only medication with indication acute treatment of bipolar depression. The use of standard antidepressants to treat bipolar depression is controversial and the evidence base is inconclusive (Pacchiarotti et al., 2013, Sidor and Macqueen, 2011, Taylor et al., 2014, Yatham et al., 2013). Quetiapine might therefore be more likely to be prescribed to patients with predominantly depressive episodes, which is mostly the case in bipolar II disorder. Hence, a possible increased prescription of drugs with antidepressant profile (such as lamotrigine or quetiapine) might stem from changes in case-mix or diagnostic shifts with respect to bipolar subtypes.

Bipolar disorder has received increased attention in the 2000s, not least because of the launching of new treatments. It is not known if this has affected the prescription pattern. The purpose of this study was therefore to study possible changes in the prescription of mood stabilizers and antidepressants for bipolar disorder during the period 2007–2013.