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BIPOLAR DISORDER
What is bipolar disorder?
Formerly known as manic depression, bipolar disorder is a
condition involving severe mood swings, from periods of elation
and agitation (mania) to episodes of profound depression.
Psychotic symptoms (hallucinations, delusions) are common, as
is anxiety. Episodes of depression are usually more common than
episodes of mania, and bipolar disorder is often misdiagnosed as
unipolar depression (see Depression), at least initially. This may
have serious consequences, as antidepressant treatment by itself
may provoke an episode of mania.
Mania typically results in severe disturbance of normal life and
relationships. A less severe form (hypomania) may occur instead
that does not cause major functional impairment. A distinction is
often made between bipolar I disorder (mania + depression) and
bipolar II disorder (hypomania + depression), but treatment is
required in both cases. In this section, the term bipolar disorder
refers to the more serious bipolar I disorder, unless stated
otherwise.
The course of bipolar disorder is very variable. Some people with
bipolar disorder experience more than four episodes of mania or
hypomania or depression in a year, which is known as rapid
cycling. Others may have extended periods of normal mood
(remission) between episodes. Bipolar disorder is more likely than
unipolar depression to require referral for specialist, hospital-based
treatment, and manic episodes in particular are a prominent cause
of hospital admission.
The causes of bipolar disorder, like those of depression and
anxiety, are not well established. There is clear evidence that the
disorder runs in families, but inheritance is not simple and there
are likely to be many genes that contribute to susceptibility. Major
life events and childhood trauma/abuse, which are thought to be
important predisposing factors in unipolar depression, appear to
play a smaller role in bipolar disorder. Abnormalities in levels of
neurotransmitters in the brain are important, as in unipolar
depression, although it is thought that the neurotransmitter
dopamine is likely to be most involved in bipolar disorder,
rather than noradrenaline or serotonin levels.
Who does bipolar disorder affect?
Bipolar disorder is less common than unipolar depression and is
thought to affect about 0.5 per cent of the population over the
course of a lifetime. Onset of symptoms usually occurs slightly
earlier than in depression, peaking between the ages of about
15-25 years. Its prevalence appears to be about the same in men
and women.
Present treatments and shortcomings
The treatments currently authorised in the UK for the treatment of
acute mania are lithium salts and semisodium valproate
(Depakote, sanofi-aventis). A further medicine may be added if
response to lithium is insufficient. Those most often used are
olanzapine (Zyprexa, Lilly), quetiapine (Seroquel, AstraZeneca)
and risperidone (Risperdal, Janssen-Cilag). Lithium, valproate and
olanzapine are also used for long-term prevention of recurrence
after a manic episode. If these are not sufficient, the anti-epilepsy
medicines carbamazepine (Tegretol, Novartis) or lamotrigine
(Lamictal, GSK) may sometimes used, although the latter is not
currently authorised for this purpose.
Episodes of depression in bipolar disorder are treated using
antidepressants, and a selective serotonin reuptake inhibitor (SSRI;
(see Depression) is recommended initially. However, it is important
that an anti-manic medication should be given at the same time,
to avoid the risk of switching into an episode of mania, or
accelerating the rate of cycling, which may happen if
antidepressants are used alone. For similar reasons, the
antidepressant is usually discontinued after resolution of the
depressive episode and not continued long-term.
Tremor, sedation, dizziness, weight gain, nausea and other
gastrointestinal symptoms are among the most common adverse
effects experienced during treatment with the main anti-manic
medications. These may be troublesome enough to limit the dose
that can be given or to make some people stop taking their
medication. Sudden stopping (or erratic use) of lithium, for
example, may result in a recurrence of mania. Weight gain
may increase the risk of developing diabetes, or may worsen
pre-existing diabetes. For such reasons, newer medications
with fewer and milder side-effects would be desirable for the
management of bipolar disorder.
Following resolution of an acute episode, some forms of
psychological therapy may also be helpful in addition to the use of
medication. Psychosocial support (befriending) and participation in
self-help groups may also be appropriate.
What's in the development pipeline?
Advanced projects for developing new treatments for bipolar
disorder largely involve extensions to uses of existing medications.
For example, quetiapine (Seroquel, AstraZeneca) is already
available for the treatment of acute mania, and is now in Phase 3
study for use in managing acute depressive episodes and for the
maintenance of remission. A sustained release formulation is
also in Phase 3 trials. Risperidone and topiramate (Topamax,
Janssen-Cilag) are also undergoing Phase 3 studies that would
broaden their uses. In addition, Lilly is studying a new
combination (Symbyax) of olanzapine and the SSRI fluoxetine in
bipolar depression. While these initiatives may be seen to some
extent as a verification of existing practice, they are nonetheless
important for putting treatment on a more secure basis, as bipolar
disorder has been less extensively studied in the past than unipolar
depression.
New compounds in development include licarbazepine (Novartis),
which is in Phase 3 trial for acute mania, an extended release form
of paliperidone (Johnson & Johnson), a derivative of risperidone,
also in Phase 3 trial, an oral form of uridine (RG2417) and
triacetyluridine (RG2133, RepliGen), in Phase 2 trial, and, at
Phase 1, a derivative of valproate (DP-VPA, D-Pharm) which has
been developed to have a better side-effect profile than valproate
itself. In addition, Forest Labs has RGH-188 at the same stage, and
Memory Pharma is testing MEM 1003 (Phase 2) for control of
acute mania.
FOR FURTHER INFORMATION CONTACT:
MDF - The BiPolar Organisation
Castle Works, 21 St George's Road
London, SE1 6ES
Phone: 0845 634 0540 (Helpline)
Website: www.mdf.org.uk
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