Treating bipolar disorder

• Introduction

• Treatment for bipolar illness

• Drug treatments

• Mood stabilizers

• Antidepressants

• Antipsychotics

• Talking treatments

• ECT

• The future

Introduction

Drug treatment, in combination with professional support and counselling and education for the family (see section 7 - Talking treatments) can reduce the frequency and severity of manic and depressive episodes, and allow people with bipolar illness to get on with their lives. But some people don't respond to existing drug treatments, and many have to endure unpleasant side-effects. Future research in bipolar illness is designed to tackle these problems.

This section covers the advantages and disadvantages of current treatments for bipolar illness and considers some future approaches.

Treatment for bipolar illness

Because symptoms of bipolar illness can range from mild depression to severe delusions and hallucinations, treatments need to be tailored to the individual. ¹ Bipolar illness is hard to treat because symptoms fluctuate. For example, symptoms of mania could be successfully treated, but the depression may remain.

The initial approach to treatment usually depends on what symptoms are most prevalent. If someone is currently depressed, that will be treated first. If a doctor subsequently decides the person has bipolar illness, he or she will usually prescribe mood stabilisers. Other therapies - for example antidepressants - or psychological treatments such as cognitive behavioural therapy may be used alongside mood stabilisers.

Bipolar treatments can be acute - intended to relieve symptoms in the short term (for example during a manic episode), or prophylactic - provided over the long term as maintenance therapy and intended to prevent symptoms from recurring.

In an ideal world, drug treatments should be used in the context of family support and counselling or psychotherapy for people with bipolar illness. Many experts now recognise that talking therapies can improve the symptoms of bipolar illness as well as help people to live with their condition (see section 7).

Drug treatments

Mood stabilisers

Lithium

Litihium is the oldest treatment for bipolar illness - it has been used for over 50 years. It remains the first choice for doctors aiming to stabilize mood, as it is effective for around 60% of people.

Despite its long history, researchers are still unclear how lithium works. Studies have found that lithium has a range of effects in the brain; it raises (and lowers) levels of chemicals such as inositol phosphates. ^{2a 2b}

Lithium also reduces levels of an enzyme called PKC ^{3a 3b} that plays a vital role in the processing of nerve cell signalling, and other studies suggest that lithium increases the amount of grey matter in the brain. These findings may ultimately shed light on how lithium works in bipolar illness.

Lithium has its drawbacks. It is not effective for 20-40% of people, especially those with dysphoric mania and mixed states. It has a narrow therapeutic range (a toxic dose is not much bigger than a therapeutic one). Lithium can cause lethal changes in electrolyte and fluid balance in the body. Lithium can take up to a week to effectively stabilise mood.

Lithium can also have severe side-effects, ⁴ including:

• weight gain
• tremor
• acne
• muscle weakness
• cognitive defects, such as confused thought processes
• kidney problems (manifesting as polyuria - increased frequency/volume of urine, polydipsia - excessive thirst). Severe kidney problems are rare but serum creatinine levels are measured regularly during lithium treatment to give doctors an idea of whether the kidneys are still working as they should. ⁵

The unpleasant side-effects experienced can make some people stop taking the drug. But stopping lithium can cause withdrawal effects such as 'rebound mania'. Also, if people restart treatment after withdrawing from lithium, they may become resistant to its benefits. For these reasons, psychiatrists recommend that people stay on lithium for at least 2 years before they consider discontinuing treatment.

"I have been on Lithium for a year now and I wouldn't change medicines for anything else"

"Lithium may work for some, for me it was disaster. Mental confusion, unable to concentrate, acne, which has not gone away after two years, enlarged thyroid and hypothyroidism. It did nothing for my bipolar II disorder"

Responses taken from bipolar.about.com/health/bipolar/library/qa/bl-qa-lithium-work.htm

Anticonvulsants

Anticonvulsants are traditionally used for treating epilepsy. They have also proved useful in bipolar disorder for people who don't respond to lithium (or who cannot tolerate its side effects). When combined with carbamazepine or divalproex, lithium can work for people who previously did not respond to it.

Anticonvulsants can be a first-line treatment, especially for people who have mixed or dysphoric bipolar states. ⁷ One study ⁸ suggested that people with a history of substance abuse were more likely to benefit from this drug than lithium.

Researchers are still unclear how anticonvulsants improve symptoms of bipolar illness. Studies have shown that in rat brains, divalproex, like lithium, reduces levels of PKC. ⁹

Carbamazepine and divalproex can have quite severe side effects. Some of these are given below:

• nausea, vomiting and indigestion are commonly reported, but usually wear off after a few doses
• drowsiness
• headaches
• confusion/dizzinessv
• skin irritation
• weight gain
• liver reactions leading to jaundice and blood cell disruption
• hair loss or thinning occurs in a minority of patients. Dietary supplements of selenium and/or zinc may help
• cognitive side effects such as double vision and difficulty concentrating

Newer anticonvulsants - gabapentin and lamotrigine - may be effective alternatives to carbamazepine and divalproex. These drugs may have less severe side effects, although of course they have some side effects. Gabapentin has been linked with weight gain and hypotension. These drugs are undergoing clinical trials and their use in bipolar illness has not yet been approved.

Antidepressants

Antidepressants are usually given to treat depression in bipolar illness. However, they can make bipolar illness worse by causing rapid cycling or mania in people who are also on mood stabilisers. Tricyclic antidepressants may be particularly bad in this respect, and are not generally used in bipolar illness.

See Treatment of depression for more information on antidepressants

If antidepressants are given on their own, side effects may be mild, but if they are given in combination with other drugs, drug interactions can mean side effects are more severe.

Antipsychotics

In an acute manic episode, psychotic symptoms such as hallucinations and delusions can be unpleasant and disruptive for someone with bipolar illness, and their family and friends. Lithium takes up to a week to take effect, so antipsychotics (also known as neuroleptics or major tranquillisers) may be given to improve manic symptoms in the meantime.

Antipsychotics may also be prescribed long term as maintenance therapy in bipolar illness. Clozapine, olanzapine or risperidone in combination with lithium have been studied as both maintenance therapies and in the management of 'breakthrough' episodes'. ¹⁰ Olanzapine has been licensed for bipolar in the USA and New Zealand and it's likely that in the UK other antipsychotics will soon be licensed for maintenance therapy in bipolar disorder.

See Treatment of schizophrenia for more information on antipsychotics

With the older typical antipsychotics (e.g. haloperidol), one in three people experience problems with movement and co-ordination called extra-pyramidal effects (EPS). Other side effects associated with typical antipsychotic drugs include persistent depression, irritation, dry mouth, constipation, and hormonal disturbances.

Atypical antipsychotics such as clozapine, risperidone and olanzapine may be given as alternatives to the typical antipsychotics. They produce fewer or no extra-pyramidal effects, but have side effects of their own. In rare cases, clozapine can cause potentially fatal immune system dysfunction; both clozapine and olanzapine are associated with weight gain.

For more information, see Treatment of schizophrenia

According to researchers, drug treatment alone puts off but does not prevent relapses of bipolar illness. About 40% of people relapse in a one-year period, 60% in two years and almost 75% in five years. ¹¹

Talking treatments

Psychological therapies or talking therapies, in addition to drug treatment, can give people ongoing support and help them recognise situations that might trigger off a relapse of the illness.

A range of different approaches can be helpful for people with bipolar illness. These include counselling, cognitive behaviour therapy, and psychotherapy. These approaches can help people rebuild their family and social relationships, and help them come to terms with their condition.

While people with bipolar illness say they find talking treatments helpful, and professionals agree they are needed, ¹² there is not much published research assessing their effectiveness. It is not clear which types of talking therapy are most effective, or at which stage in the illness they should be used.

Personal reactions

"As good and as supportive as my Psychiatrist may be, I still feel that I need more support: a structure that will teach me coping skills, ways of dealing with my illness and helping me to regain my independence."

Gail's story - read more...

ECT

If someone with psychotic depression doesn't respond to any other therapy, or if they continue to have episodes that 'breakthrough' despite ongoing drug treatment, electro-convulsive therapy (ECT) and may be given. ¹³

Hopkins and Gelenberg (1994) also reported limited success with light therapy. This treatment involves ultra violet light, which has been found effective for some people with Seasonal Affective Disorder (SAD); a depression coming on during the winter months.

The future

New drug approaches

Calcium channel blockers for the treatment of acute mania have received interest as adjuncts to traditional mood stabiliser treatments. Nimodipine has been studied in people with rapid cycling bipolar illness, but more clinical trials are needed.

PKC could be a useful target for new drugs. The fact that lithium and divalproex, (two chemically unrelated drugs), inhibit PKC, suggests that it might be important for bipolar illness. Researchers believe it may lead to new treatments.

For example, Bebchuk et al (2000) conducted a small study of tamoxifen, a well-established anti-cancer drug that also blocks PKC, in bipolar illness. Tamoxifen was effective in five out of seven people and was well tolerated, with only one person reporting any adverse effect.

Doctors are also increasingly using combinations of mood stabilisers for bipolar illness.

New thinking

Aside from the development of new drugs, future approaches to treating bipolar illness may rely on new ways of thinking about treatment and even the nature of the condition.

The role of talking therapies for bipolar illness is becoming increasingly recognised.

Studies suggest that people who later turned out to have bipolar depression were initially diagnosed with unipolar depression and prescribed antidepressant drugs. Accurate diagnosis is essential for effective treatment, so an increased awareness of the condition (amongst the medical profession and amongst the general population) may improve treatment.

Mark Waterlow - February 2001