Bipolar Disorder

Treatment

The treatment of bipolar disorder is difficult, due to the complexity and variability of the illness and the effect of the disorder on cognition, judgement 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); with a view to rapid and effective amelioration of acute episodes, preventing recurrences of episodes, enhancing social interpersonal and vocational functioning and decreasing the incidence of suicidal acts (Young et al, 2000).

Pharmacotherapy

Medications commonly used for the treatment of bipolar disorder are summarised in the table below (table adapted from Keck, Jr. et al, 2001).

Lithium
Lithium is a well established treatment for bipolar disorder, being effective in the treatment of both the manic and depressive phases (Compton & Nemeroff, 2000; Licht, 1998). Recent reviews from both the UK and the USA, including the Expert Consensus Guidelines, 1998, reported that lithium is the first-line therapy for patients with bipolar disorder, with an approximate response rate of 79% (Compton & Nemeroff, 2000).

Patients on lithium therapy should have both their serum lithium concentration and thyroid function monitored, and 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).

Anticonvulsants
The treatment spectrum for bipolar disorder has broadened since the introduction of the anticonvulsants, which include carbamazepine, valporate and lamotrigine. Patients with rapid cycling or mixed episode are more likely to benefit from treatment with anticonvulsants than patients with other types of bipolar disorder (Muller-Oerlinghausen et al, 2002).

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 cycles. 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).

Valporate 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 valporate 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 valporate treatment did not differ from that of placebo when prolonging 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 valporate 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 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 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 valporate in bipolar disorder, however there is a risk of 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, however, more research is needed to clarify its position within the treatment spectrum.

Antidepressants
Standard antidepressants are effective for the treatment of bipolar I disorder, in combination with a mood stabiliser. The most commonly recommended antidepressants are selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and bupropion (Compton & Nemeroff, 2000).

Read more about the use of antidepressants

View an animation on the mechanism of action of SSRIs

Psychotherapy

Bipolar disorder patients have a relatively high rate of nonadherence to pharmacotherapy, estimated at 32–45% of treated patients (Rothbaum & Astin, 2000). This 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 to reduce the patients’ suicide risk. There are different psychotherapeutic approaches, which are appropriate to 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 main aim of CBT is to alter the negative thoughts of a patient with bipolar disorder. This form of therapy focuses not only on the behaviour of the patient, but their cognitions; what the person thinks about, how they perceive things and how they interpret what is happening to them. CBT tries to alter these negative thoughts by teaching patients to understand how their thinking patterns contribute to their symptoms and how to change their thoughts and behaviour so that symptoms are less likely to occur (U.S.Department of Health and Human Services, 1999). It also informs them about the social-functioning difficulties associated with the disease and how to self-monitor the occurrence, course and severity of the disorder in order to make appropriate therapeutic interventions. Patients are taught to remove any obstacles to adherence and are provided with nonmedical, behavioural strategies for coping with the consequences of mania and depression. Specific coping-strategies are taught for specific symptoms; for example patients with impaired concentration are advised to reduce noise and overstimulation and to concentrate on one thing at a time and patients with extreme mania are taught relaxation techniques (Rothbaum & Astin, 2000).

Psychoeducation
The need for better education regarding bipolar disorder has long been recognised. By providing patients and their families with information on bipolar disorder, psychotherapy aims to promote treatment adherence and dispel stigma, to promote avoidance of drug abuse and to teach patients how to identify relapse symptoms (Maj et al, 2002). The main focus of psychoeducation is the side effects of treatments, the course of the illness and barriers to recovery (Maj et al, 2002; Rothbaum & Astin, 2000).

The results of investigations into the effectiveness of psychoeducation are promising. The majority of psychoeducational interventions result in improved treatment adherence and 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
Normal marital and family interactions are often difficult for patients with bipolar disorder. As a result of their strained relationships patients with bipolar disorder may have increased relapses and poor functioning. Family therapy aims to educate patients and their families about bipolar disorder with a view to increasing adherence to prescribed medication; improving the patient’s acceptance of the illness; enhancing social and occupational functioning; and managing stressors. Families are trained in communication skills and family therapy tries to restore functional family relationships after a mood episode. The family therapy sessions also seek to address any post-traumatic symptoms that the patient and their family may have after an acute attack or period of hospitalisation.

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).

Group Therapy
Bipolar disorder group therapy has only been used in the last 10–15 years, as bipolar patients were traditionally considered unsuitable for this type of therapy. However, recent studies have shown that group therapy educates patients about treatment compliance, the number of relapses can be reduced by 15% by decreasing the stigma associated with bipolar disorder (Rothbaum & Astin, 2000). Patients who have combined group treatment and medication can have a less severe course of disease than patients who receive medication alone in terms of poor family interactions, marital failures and the need for readmission to hospital. While data can be difficult to compare, due to differences in the therapy used, the data generally support the use of group therapy for bipolar disorder patients (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).

Novel Options

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).