Bipolar Disorder


Bipolar Disorder is the medical name for manic depression, and means
an illness with ‘directly opposite’ states of mind. Sufferers of
Bipolar illness have mood swings, sometimes feeling ‘high’ or manic,
and at other times feeling ‘low’ or depressed. Although the ‘highs’
can occasionally be enjoyable, these extreme emotions are often
distressing and can be very disruptive to people’s lives.

Few Disorders in history have been described with such consistency as
Bipolar Disorder has been. Symptoms that characterise the illness can
be found in medical literature throughout the centuries from the
ancient Greeks to present day.

A sufferer of Bipolar will experience mood swings of two extremes,
mania and depression, the extent to which these moods will affect the
sufferer is determined by the severity of the illness. The
distinction between Bipolar Disorder and Unipolar Disorder sufferers
is the absence of mania in an individual who suffers from Unipolar
Disorder or clinical depression. Common symptoms for both illnesses
include:

· Feeling sad or unhappy with no identifiable causes, or known as
Endogenous Depression.

· Lack of interest in activities usually enjoyed.

· Insomnia or excessive periods of sleep.

· Little energy.

· Experience of medical problems or difficulty concentrating.

· Loss of libido.

· Social withdrawal.

· Loss of self confidence.

· Suicidal thoughts.

· Changes of attitude.

The symptoms which determine an individual suffering from Bipolar
Disorder during manic episodes can also include:

· Having lots of energy.

· Poor Judgement.

· Self centeredness.

· Be extremely active and talkative.(rapid pressurised speech)

· Feel extremely happy or sometimes extremely angry.

· Feel restless and irritable.

· Have racing thoughts. (If these thoughts are strange or unfounded
they are called delusional)

· Insomnia.

· Sometimes hear voices or see things that aren’t there. (called
hallucinations)

· Increased interest in sex or sexual behaviour which is unusual for
an individual.

Bipolar Disorder has been divided into two sub types (Dunner et al
1976). Bipolar I sufferers are diagnosed with mania which is severe
enough to require treatment, psychosis in these instances are
frequently evident in manic episodes as are periods of rapid cycling
from one emotional extreme to the other. Bipolar II sufferers
experience episodes of hypomania but not acute enough to require
hospitalisation, This classification for the milder forms of Bipolar
have however been inconsistent and so to eliminate such ambiguity a
system to distinguish the milder forms of mania were proposed (Angst
1978). Bipolar patients were divided into Md and mD, with M (Mania)
and D (Depression) indicating an episode which required
hospitalisation and m and d describing behaviour that could clearly
differentiated from normal behaviour but not severe enough to merit
hospitalisation.

Suggestions into the causes for Bipolar vary throughout the different
psychological approaches. One of the strongest theories lie in the
suggestion that the disease is strongly associated with the biological
make up of the brain and the role neurochemicals play.

Brain-imaging studies are helping scientists learn what happens in the
brain to produce Bipolar Disorder and other mental illnesses. Certain
brain-imaging techniques allow researchers to take pictures of the
living brain at work, to examine Its structure and activity, without
the need for surgery or other invasive procedures. These techniques
include magnetic resonance imaging (MRI), positron emission tomography
(PET), and functional magnetic resonance imaging (fMRI). There is
evidence from imaging studies that the brains of people with Bipolar
Disorder may differ from the brains of healthy individuals. As the
differences are more clearly identified and defined through research,
scientists will gain a better understanding of the underlying causes
of the illness, and eventually may be able to predict which types of
treatment will work most effectively.

The neurotransmitter system has received a great deal of attention as
a possible cause of Bipolar Disorder. Researchers have known for
decades that a link exists between neurotransmitters and mood
Disorders, because drugs which alter these transmitters also relieve
mood Disorders. Some studies hypothesize that a low or high level of
a specific neurotransmitter such as serotonin, norepinephrine or
dopamine is the cause. Others indicate that an imbalance of these
substances is the problem - i.e., that a specific level of a
neurotransmitter is not as important as its amount in relation to the
other neurotransmitters. Still other studies have found evidence that
a change in the sensitivity of the receptors on nerve cells may be the
issue. In short, researchers are quite certain that the
neurotransmitter system is at least part of the cause of Bipolar
Disorder, but further research is still needed to define its exact
role.

Our genes hold all of our hereditary information and provide the
“genetic code” that allows our bodies to function, but our environment
can affect how our genes function. Half of our genes are inherited
from our mothers and half from our fathers. When looking at genes in
the context of Bipolar Disorder, genes may confer predisposition to
certain symptoms rather than the Disorder itself. For example, with
Bipolar Disorder they look at susceptibility to mania or depression
rather than mood Disorders as a whole.

Population studies, twin studies, and adoption studies were all
reviewed for their findings regarding the role of genetics in Bipolar
Disorder. The higher rates of Bipolar Disorder among relatives,
identical twins, and biological parents relative to adoptive parents
were all cited as evidence of the role of genetics. These higher risks
compare to Bipolar Disorder occurring in roughly one percent of the
population as a whole.

In population studies they found that there is a 10 percent risk that
others in the nuclear family (father, mother, siblings) will have the
Disorder once one family member is diagnosed. Second degree relatives,
such as grandparents, uncles, and aunts were found to have a four
percent risk.

Twin studies looked at the question of when one twin has Bipolar
Disorder, how often does the other twin also have the Disorder? With
identical (monozygotic) twins, this was found to be true 60 percent of
the time. With fraternal (dizygotic) twins, the frequency was found to
be 10 percent, the same as that for traditional siblings.

Adoption studies compared the rate of Bipolar Disorder in biological
and adoptive parents of adoptees with Bipolar Disorder. Biological
parents share the genes of the afflicted person, while the adoptive
parents share the same environment. The incidence of Bipolar in the
biological parents of adoptees with Bipolar Disorder was 18 percent,
while the rate of concurring Bipolar Disorder in adoptive parents was
roughly 7 percent.

After presenting the compelling genetic evidence, it was concluded
that genetic factors alone do not determine susceptibility to Bipolar
Disorder. The risk for Bipolar Disorder stems from a complex mix of
both genetic and environmental factors, and their current theory is
that most individuals who develop these conditions must have several
risk genes and significant environmental influences. It has also been
illustrated that the current line of thought is that Bipolar Disorder
represents not a single gene Disorder, but a complex issue involving
multiple genes.

Researchers concluded: "As defined by the DSM-IV, Bipolar affective
Disorder is highly heritable. There are substantial genetic and non
shared environmental correlations between mania and depression, but
most of the genetic variance in liability to mania is specific to the
manic syndrome."

The primary psychological culprit implicated in the manifestation of
Bipolar Disorder is stressful life events. These can range from a
death in the family to the loss of a job, from the birth of a child to
a move. It can be pretty much anything, but it cannot be precisely
defined, since an event which presents it’s self as stressful to one
individual may not affect another. With that in mind, research has
found that stressful life events can lead to the onset of symptoms in
Bipolar Disorder. However, once the Disorder is triggered and
progresses, "it seems to develop a life of its own. Once the cycle
begins, a psychological or pathophysiological process takes over and
ensures that the Disorder will continue”.

When we look for the cause of Bipolar Disorder, the best explanation
via the research available at this time is what is termed the
"Diathesis-Stress Model." The word diathesis means, in simplified
terms, a bodily condition that make a person more than usually
susceptible to certain diseases. Thus the Diathesis-Stress Model says
that "each person inherits certain physical predispositions that leave
him or her vulnerable to problems that may or may not appear,
depending on what kinds of situations that person confronts." Durand
and Barlow define this model as a "hypothesis that both an inherited
tendency and specific stressful conditions are required to produce a
Disorder."

The psychodynamic approach to the causes of depression look at the
relationships sufferers had with their parents in early childhood. It
has been suggested that unresolved conflicts or emotional pain
associated with in these relationships can manifest n adulthood to
cause self hatred, low self esteem and other negative emotions
associated with depression. The psychodynamic approach associates
itself only to the causes of unipolar and does not explain the manic
symptoms displayed by those individuals suffering from Bipolar
Disorder, It also fails to explain the many people who suffer from
chronic depression who assure psychiatrists their childhoods were
happy.

In conclusion to identifying the causes of Bipolar Disorder it seems
apparent that no one cause can be identified. It is more probable
that a number of the causes discussed above contribute to the
condition however research continues.

Although Bipolar Disorder can become disabling, it is also among the
most treatable of the mental illnesses. The combination of
psychotherapy and medications returns the vast majority of
manic-depressive patients to happy functioning lives. Bipolar
treatments can be acute – intended to relieve symptoms in the short
term, such as intense drug treatments and ECT (i.e. during a manic
episode), or prophylactic – provided over the long term as maintenance
therapy and intended to prevent symptoms from reoccurring e.g.
Cognitive Behavioural Therapy.

The most common medication used in treating Bipolar Disorder are the
mood stabilising drugs in particular Lithium Carbonate. Lithium which
has been prescribed for over fifty years , successfully reduces the
number and intensity of manic episodes for seventy percent of those
who take medications. Twenty percent become free of symptoms. Those
who respond best to Lithium are patients who have a family history of
depressive illnesses and whom have periods of relatively normal mood
between their manic depressive phases. Very effective in treating the
manic phase, lithium also appears to prevent repeated episodes of
depression. One theory for this is that in controlling the mania,
lithium helps prevent the swing into depression.

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.

Lithium also reduces levels of an enzyme called PKC 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, including:

· Weight gain.

· Tremors.

· 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.

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. For
other drugs currently used to treat Bipolar Disorder please refer to
appendix A.

In situations where medication, cognitive therapy or alternative forms
of treatment for Bipolar have been found ineffective for a patient the
use of ECT or electro convulsive therapy is an option. Used when the
Disorder is at it’s most severe and particularly when suicidal
thoughts have become increasingly prominent this form of treatment is
considered appropriate and effective.

The procedure for administering ECT involves:

· Procurement of a patient consent form.

· Pre-treatment evaluation – a complete physical examination is given
to ensure the patient has no medical conditions which might produce
complications during the procedure.

· Patient is given a general anaesthetic – so they do not feel any
pain.

· The patient is given a muscle relaxant – this prevents the patient
injuring themselves during their convulsion.

· An electric shock is applied to produce a convulsive seizure. The
shock is typically between 140 – 170 volts and lasts between 0.5 and
1 second. The shock is applied in one of two ways. In bilateral ECT
two electrodes are attached so that the shock is delivered to both
brain hemispheres. In unilateral ECT (Goldman 1949) a single
electrode is attached to the not dominant hemisphere, so that only one
hemisphere is shocked. The later reduces the unwanted cognitive side
effects of ECT (Squire & Slater 1978) but studies have shown it to be
less successful in actually treating the depressive Disorder.

· A typical course of treatment consists of between 6 and 12 actual
shocks, given over a period of 2 to 3 weeks.

· After treatment the patient is typically given a course of anti –
depressants to reduce the likelihood of relapse.

Shock treatment to the brain induces a grand mal seizure in the
brain. Seizures are similar to Epileptic convulsions in which the
brains electrical pathways all fire at the same time. The seizures
alter many chemical aspects of the brain both during and after seizure
activity.

In a review of the clinical literature the conclusion has been made
that ETC is a very effective treatment for specific Disorders, at
least in the short term, with success rates of 60% - 80%. The main
advantages of ETC are that it:

· Works on patients that have failed to respond to other types of
therapy.

· Produces positive effects far more quickly compared to other
treatments. (Within weeks compared to months).

· Can be used in cases where drug therapy is not appropriate e.g.
pregnant women or patients who suffer severe reactions to anti
depressants.

TMS is an alternative to ECT that's in the final stages of
development. This procedure involves transmitting magnetic, rather
than electrical, impulses to the brain.

Although the initial response to ETC is good there is a fifty per cent
relapse rate within six months unless anti depressants or further ECTS
are given as follow up treatments. The side effects during ETC
include increased blood pressure and pulse as well as irregular heart
beat. There is a small risk of associated death (1 in 100, 000). If
the patient aspirates (breathes in) or saliva or vomit during
treatment they could develop pneumonia. In around 1 in 2, 000
treatments patients experience spontaneous seizures at the end of the
treatment. Post treatment side effects include Retrograde amnesia,
impaired ability to form new memories, sleep disturbances and
disorientation and confusion.

One of the main criticisms of ECT is that there is no convincing
scientific explanation of how it works, only a number of
unsubstantiated theories. The Neuropsychological theory suggests that
ECT stimulates the long term production of neurotransmitters, thus
acting like a prolonged course of anti depressants. Another theory
which attempts to discredit ETC claims that the shock administered
causes brain damage which disrupts memory engrams. This causes the
patient to temporarily forget their problems. (Breggin 1979) The
Punishment hypothesis is based on evidence from ‘sham ETC’ where
patients are taken through the whole procedure but are not actually
given any shock. It suggests that patients see the treatment as a
punishment for their current behaviour and stop ‘acting’ depressed to
avoid further punishment. The evidence for this is weak as nearly all
studies show that patients who receive real shocks show far greater
improvements. (West 1981)

CT and MRI scans taken before and after ECT show no structural changes
to the patients brain.

As outlined, Any patients preparing to undergo ECT should give
informed consent. Ethical issues can arise when a person is suffering
such a severe depressive episode it is questionable if he or she can
give informed consent. This is a paradox, as it is only these
patients who really require this level of treatment.

ETC is widely considered to be an appropriate treatment for those
patients whom have exhausted all other possibilities and are still
suffering from Bipolar to an extent that their lives are being
debilitated by the Disorder. It is also appropriate for individuals
who are at a high risk of suicide, this is because the positive
effects are rapid.

As an addition to medication, psychosocial treatments—including
certain forms of psychotherapy (or "talk" therapy)—are helpful in
providing support, education, and guidance to people with Bipolar
Disorder and their families. Studies have shown that psychosocial
interventions can lead to increased mood stability, fewer
hospitalisations, and improved functioning in several areas. A
licensed psychologist, social worker, or counsellor typically provides
these therapies and often works together with the psychiatrist to
monitor a patient's progress. The number, frequency, and type of
sessions are based on the treatment needs of each person.

Psychosocial interventions commonly used for Bipolar Disorder are
cognitive behavioural therapy, psycho education, family therapy, and a
newer technique, interpersonal and social rhythm therapy. Researchers
are studying how these interventions compare to one another when added
to medication treatment for Bipolar Disorder.

Cognitive behavioural therapy helps people with Bipolar Disorder learn
to change inappropriate or negative thought patterns and behaviours
associated with the illness. Psycho education involves teaching people
with Bipolar Disorder about the illness and its treatment, and how to
recognize signs of relapse so that early intervention can be sought
before a full-blown illness episode occurs. Psycho education also may
be helpful for family members.

Family therapy uses strategies to reduce the level of distress within
the family that may either contribute to or result from the ill
person's symptoms. Interpersonal and social rhythm therapy helps
people with Bipolar Disorder both to improve interpersonal
relationships and to regularize their daily routines. Regular daily
routines and sleep schedules can help protect against manic episodes.

St John's Wort is a herbal remedy, also known as hypericum. It has
been used for centuries for depression and anxiety. It is commonly
used in Germany and other parts of the world. The flowers and leaves
of the St John's Wort plant (Hypericum perforatum) are used to make
the herbal remedies. These flowers and leaves contain many different
compounds including hypericin, which is thought to be one of the
compounds that makes St John's Wort helpful for depression and
anxiety. These compounds are extracted from the plant matter using
alcohol.

St John's Wort looks very promising as a treatment for mild to
moderate depression. There have been comparisons of St John's Wort
with other medicines for depression such as imipramine and
amitriptyline (tricyclic antidepressants) in tests. These studies have
been fairly positive for St John's Wort, indicating that St John's
Wort helps with depression and does not have many side effects.

It is not known how St John's Wort works. It is thought that it may
affect serotonin, Noradrenaline and dopamine uptake. Trials into its
effectiveness of treating depression have been only for short periods
of time (e.g. 4 or 8 weeks), so it is not certain how well St John's
Wort will work or whether there will be more side effects over a
longer period of use. These studies have usually been carried out with
only small numbers of patients, which is also a disadvantage.

St John's Wort has been compared with older tricyclic antidepressants
(e.g. imipramine and amitriptyline), and has generally shown fewer
side effects than the tricyclic antidepressants. It would be useful to
compare St John's Wort with newer antidepressants such as fluoxetine
(Prozac) and paroxetine (Aropax) to see if St John's Wort works as
well and if St John's Wort has as few or less side effects, as these
medicines are used so commonly now.

This remedy does not seem to have many problems with side effects,
however possible side effects are listed below:

· Allergy.

· Increased skin sensitivity to the sun is extremely rare.

· St John's Wort generally does not seem to cause drowsiness and
affect the ability to drive, however a very small percentage of people
taking it may feel tired.

· Increased sensitivity to touch, temperature and pain is a
possibility.

Likely interactions include (but are not limited to):

· Certain antidepressants including fluoxetine (Prozac), paroxetine
(Aropax), other SSRI antidepressants.

· Warfarin/coumarins/anti-coagulants (for thinning the blood).

· Digoxin (for the heart).

· Cyclosporin (for transplants and some diseases such as psoriasis and
arthritis).

· Theophylline (for asthma).

· Migraine medicines called triptans, e.g. Imigran (sumatriptan).

· Some medicines used to treat HIV.

· Oral Contraceptives ("the pill").

· It is also thought possible that there could be an interaction with
some epilepsy medicines that sometimes are also used for pain, or
Bipolar Disorder e.g. carbamazepine, phenytoin, and phenobarbitone.

It is very likely that there are other interactions that are not yet
known.

It is possible that this form of treatment could be helpful for
sufferers of moderate unipolar or for individuals who are successfully
managing the depressive elements of Bi Polar but due to the severity
of symptoms associated with Bipolar, relief of symptoms whilst using
St Johns Wort would be rare. As mentioned before, how this treatments
works has not been addressed and the number of medications which could
be affected by the use of this treatment make it an ineffective method
of managing Bipolar Disorder.

Each form of treatment has it’s drawbacks but effectively prescribed
and used in conjunction with one another, the management of Bipolar
is successful in all but the most severe cases. If a patient is
monitored effectively and treatment tailored to the individual need
life with Bipolar can be as easy to deal with as life with out.
Appendix 1


Drugs used in the treatment of Bipolar Disorder
-----------------------------------------------

Classification

Generic name

Trade name

Uses in Bipolar illness

Mood stabilizers

lithium carbonate

Litarex, Liskonium, Li-Liquid

First-line. Effective in about 60% of Bipolar individuals in acute
manic episodes and prophylaxis.

Mood stabilisers (anticonvulsants)

carbamazepine


divalproex sodium

valproate sodium

valproic acid

Tegretol, Epitol

Depakoate (tablets)

Depakene (syrup)

Depakene (syrup)

Increasingly used as first-line, and often used for people with
Bipolar illness who do not respond to lithium, either alone or in
combination with lithium.

Novel anticonvulsants

lamotrigine

gabapentin

Lamictal

Neurontin

New compounds developed for the treatment of epilepsy, which display
some evidence of efficacy in people who do not respond to lithium. Not
yet licensed for Bipolar.

Antipsychotics

haloperidol

risperidone

clozapine

olanzapine

quetiapine


Haldol

Risperdal

Clozaril

Zyprexa

Seroquel

Prescribed with lithium in early stages of severe manic episodes; also
useful in maintenance therapyMay help with depressive as well as manic
symptoms.

Antidepressants

venlafaxine

bupropion

fluoxetine

citalopram

tranylcypromine


Effexor

Wellbutrin

Prozac

Cipramil

Parnate

Useful for depressive episodes in Bipolar illness. But certain
antidepressants and mood stabilisers may interact.

Sedative/hypnotics

lorazepam

Ativan

Sometimes used with other therapies for acute manic episodes. May help
with insomnia and anxiety associated with depressive episodes

Calcium channel blockers (not currently licensed for use in the UK)

verapamil

nimodipine

magnesium sulphate

Securon, Univer, Nimotop

May be useful supplementary therapies in the management of acute manic
episodes.


NB. This information relates to current UK practice; other countries
may have alternative treatments.


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