The treatment of bipolar disorder is difficult, due to the complexity and variability of the illness and the effect of the disorder on cognition, judgment and behaviour (Muller-Oerlinghausen et al, 2002). The American Psychiatric Association practice guidelines for the treatment of bipolar disorder recommend an integrated approach to treatment, i.e. a combination of pharmacotherapy and psychotherapy (Rothbaum & Astin, 2000). The aim is to achieve rapid and effective amelioration of acute episodes, prevent recurrences of episodes, enhance social interpersonal and vocational functioning and decrease the incidence of suicidal acts (Young et al, 2000).
Medications commonly used for the treatment of bipolar disorder are summarised in the table below (table adapted from Keck, Jr. et al, 2001).
Patients on lithium therapy should have both their serum lithium concentration and thyroid function monitored. The lithium dose should be titrated to achieve a serum concentration of 0.5–1.2 mEq/L. It often takes 6–8 weeks for a patient to achieve a therapeutic response to lithium (Compton & Nemeroff, 2000). It is still unclear whether premature discontinuation of lithium therapy actually worsens the course of the illness and there is evidence that lithium may not be adequate for the treatment of mixed states and severe mania (Licht, 1998). Patients with relatively few lifetime mood episodes, with depressive symptoms during mania, and without rapid cycling are reported to have the best response to lithium treatment (Keck, Jr. et al, 2001).
Carbamazepine, compared to lithium and placebo, is effective for the long-term treatment of bipolar disorder, but it is not approved for this indication worldwide (Compton & Nemeroff, 2000; Muller-Oerlinghausen et al, 2002). Results of several studies suggest that carbamazepine has antimanic and antidepressive properties, both as a monotherapy and in combination with lithium or antidepressants. In one study, 53% of depressed patients responded rapidly to the blind addition of lithium to carbamazepine (Compton & Nemeroff, 2000). Lithium therapy is still superior to carbamazepine, and combination therapy is better than monotherapy, especially in rapid cycling disorder. This may be due, in part, to the ability of carbamazepine to induce its own metabolism by the cytochrome P450 microsomal enzyme system (Compton & Nemeroff, 2000).
Valproate is the most frequently prescribed mood stabiliser in the USA, where it is approved for the treatment of acute mania, but only when lithium and carbamazepine have failed or are not well tolerated. While it is currently not widely used in Europe, the incidence of its use is increasing (Licht, 1998; Muller-Oerlinghausen et al, 2002; Young et al, 2000). The efficacy of valproate in the treatment of bipolar disorder is still controversial. A study in 1994 confirmed its efficacy for the treatment of mania. However more recent work in 2000 showed that valproate treatment did not differ from placebo when comparing prolongation of time to recurrence of any mood episode over 12 months (Bowden et al, 2000; Young et al, 2000). While larger trials are needed to confirm or refute these clinical data, the current thinking is that valproate is more effective for the treatment of mania than depression, but it may also have some weak-to-moderate antidepressive properties (Compton & Nemeroff, 2000).
Lamotrigine is one of a number of new and novel anticonvulsants used in bipolar disorder. It has been widely studied and its effects are thought to include inhibition of excitatory amino acids and voltage-dependent sodium channels and the blockade of serotonin 3 receptors (Berk et al, 2001). A number of studies have shown lamotrigine to be effective for the treatment of the depressive phase of bipolar disorder and rapid cycling bipolar disorder. The adverse effects of lamotrigine are similar to other anticonvulsants, with a slightly higher rate of the occurrence of headache (Compton & Nemeroff, 2000).
Lamotrigine is not practical for the treatment of the manic phase of bipolar disorder; this is partly due to the need for slow dose escalation (Berk et al, 2001; Bowden & Karren, 2002; Compton & Nemeroff, 2000). Lamotrigine has been reported to enhance the effectiveness of valproate in bipolar disorder, however there is a risk of skin rash with this dosing regimen (Compton & Nemeroff, 2000). To reduce this risk of rash a slow dosage titration is recommended. In contrast, when co-administering lamotrigine with carbamazepine a more rapid dose increase is recommended (Bowden & Karren, 2002). Lamotrigine is emerging as a potentially useful agent for the treatment of bipolar disorder, but more research is needed to clarify its position within the treatment spectrum.
Bipolar disorder patients have a relatively high rate of nonadherence to pharmacotherapy, estimated at 32–45% of treated patients (Rothbaum & Astin, 2000). Poor adherence to prescribed medication, combined with the high rates of marital conflict, divorce and unemployment associated with bipolar disorder limits the effectiveness of pharmacotherapy alone. The purpose of combining psychotherapy with pharmacotherapy is primarily to increase the patients’ adherence to prescribed medication. In addition, psychotherapy may reduce the number and length of hospitalisations and relapses, increase social functioning and improve quality of life and reduce the patients’ suicide risk. There are different psychotherapeutic approaches, which are appropriate in different stages of the disease, and they can include psychoeducation, cognitive behavioural therapy (CBT), family interventions, group therapy and therapy specific to an individual case, such as therapy for substance abuse.
Cognitive Behavioural Therapy (CBT)
The results of investigations into the effectiveness of psychoeducation are promising. The majority of psychoeducational interventions result in improved treatment adherence and lower numbers of hospitalisations and relapses. One study showed a 50% improvement in lithium compliance and a 60% decrease in hospitalisation (Rothbaum & Astin, 2000).
Family therapy is divided into three well-defined stages: an assessment stage, communication enhancement training, and problem-solving training. Families are often taught the ‘relapse drill’, enabling them to identify the signs and symptoms of a relapse and prepare them for the next episode (Rothbaum & Astin, 2000).
Electroconvulsive Therapy (ECT)
ECT is well established for the treatment of bipolar disorder, with much evidence for its efficacy in treating both the manic and depressive phases of bipolar disorder. More recently ECT has been proposed as a maintenance therapy for bipolar disorder (Berk et al, 2001). An analysis that compared studies investigating whether ECT or antidepressants are more effective for the treatment of bipolar disorder, found ECT to be more effective in 5 out of 7 studies, with ECT being more beneficial than tricyclic antidepressants (Compton & Nemeroff, 2000).
ECT should not only be considered as a last resort treatment, but also as a treatment for either the depressive or manic phase of any stage of bipolar disorder, as long as the patient is comfortable with this course of treatment. ECT should be considered as a first line therapy when patients are severely ill or are especially delusional or at a high risk of suicide. Lithium treatment is not recommended during a cycle of ECT: this combination has been reported to be neurotoxic in some cases. ECT still remains very low in most treatment algorithms, due to ongoing public concerns (Compton & Nemeroff, 2000).
Other therapeutic options that could prove beneficial in bipolar treatment include the inhibition of neuronal signal transduction systems, by omega-3 fatty acids. One small trial showed a significantly longer period of remission in patients taking omega-3 fatty acids compared to those taking olive oil. Vagus nerve stimulation and Tamoxifen have also been investigated as possible therapeutic interventions, and while preliminary research is promising, more clinical data is required (Berk et al, 2001).
Last updated: 20.12.2011