Diagnosis and Treatment for Doctors
Bipolar illness (previously called manic depressive illness) affects approximately 2% of the population, i.e. about one in ten of those who experience depression (current estimates are that 20% of the Australian population will experience at least one episode of depression.) The diagnosis is made by a patient having one or more episodes of depression, together with one or more episodes of hypomania (a term used interchangeably very often with mania). Bipolar 1 is the term for severe illness, and bipolar 2 is the term for less severe illness. “Mixed states” are where people have mainly depressive symptoms, but with some manic/hypomanic symptoms.
If possible, among the many issues GPs are asked to remember for multiple medical conditions, try to remember ask patients if they have gone through periods of 48 hours or more in which they feel unusually good, have unusual amounts of energy and in particular have much less need for sleep than usual. The combination of sleeping much less than usual, and not being tired, is a very useful diagnostic indicator. Other associated symptoms are those of much more confidence and extroversion than usual, increased talkativeness, increased social interaction and increased pursuit of pleasurable activities. The patient may be much more talkative than usual, and have far more creativity than usual.
The major risk is that the patient will drive dangerously, spend money inappropriately, or engage in undiplomatic or inappropriately sexual interactions with other people. If possible, steps should be taken to prevent these opportunities. A number of patients are also at risk of substance abuse at this time. And patients should avoid major life decisions when high or low.
Differential Diagnosis : Normal excitement /happiness in response to positive events in life, Illicit drugs . More long-term conditions are severe anxiety and ADHD.
Mania/Hypomania : High doses of major tranquillisers are usually needed, titrated downwards as people become drowsy. The choices are the older drugs (eg Largactil) or the newer atypical antipsychotics. Note that these latter agents can be used also in lower doses as long-term mood stabilisers , after the manic phase has settled
Depression and Mixed States : Antidepressants as you would usually use, plus a mood stabiliser. Avoid tricyclic antidepressants, as these are more likely to induce switching to hypomania.
Whether the patient has depression or is hypomanic, most psychiatrists believe that a mood stabilizer is important, especially during the treatment of depression , otherwise, the risk is that the patient will be oscillating rapidly between depression and hypomania.
Choice of mood stabilizer
The choices are Lithium, anticonvulsants or the atypical antipsychotics.
Lithium has a long tradition as a mood stabilizer, but there is recent realization that a number of patients may be left with renal impairment , even after stopping lithium. Lithium is also teratogenic, causing increased rates of cardiac abnormalities in particular in the foetus. Fifteen percent of people taking lithium will become hypothyroid. Lithium is best started in low dose (and serum levels require that the patient has been taking the sam e dose for one week, and that the blood test is almost exactly 12 hours after the patient last took their last dose of lithium. Ten hours to 14 hours is acceptable, but any wider time interval is undependable.) If patients are taking lithium, standard side-effects include tremor and thirst, due to a diabetes insipidus syndrome (which can be helped in many patients by Thiazide diuretics!, which will in fact cause fluid retention and increased lithium levels/lithium toxicity in some patients). Important: If stopping lithium, it is advised to do this gradually over a number of months, (while for example introducing another mood stabilizer at the sam e time), to avoid a rebound increase in frequency and severity of mood swings.
Sodium Valporate (Epilim, Valpro) is widely used as a mood stabilizer also. Common side-effects include weight gain, tiredness and hair loss. Rare problems with liver function tests and blood dyscrasias can occur, so that monitoring of blood clot and liver function is appropriate. This medication is also teratogenic .
Carbamazepine (Tegretol) is less widely used, and is perhaps less strongly supported as a mood stabilizer by formal research studies.
Lamotrigene (Lamictal) is increasingly being used to prevent bipolar depression , and sometimes to supplement the effect of anti-depressants in this illness. However, the dose can only be escalated very slowly as specified by the manufacturer, to reduce the risk of an allergic reaction, which in turn is a warning to stop the medication, to prevent the development of the potentially fatal Stevens-Johnson syndrome. Phrased differently, a rash developing on this medication is equivalent to a rash in a patient taking penicillin, with the risk of a fatal reaction if the treatment is continued. This medication does not appear to prevent mania .
(Note: You may be interested to know that the reason anti-convulsants are used to prevent bipolar disorder is that both epilepsy and bipolar disorder are illnesses which represent "kindling" in the CNS. Kindling is the process whereby the CNS learns to progressively more easily replicate abnormal electrical patterns, so that untreated epilepsy typically becomes more frequent and more severe. Similarly, untreated bipolar disorder (and indeed recurrent unipolar depression) also become more severe if no intervention takes place. Drugs which stop kindling prevent this happening as far as possible, hence the use of anti-kindling drugs/anti-convulsants.)
Zypexa (olanzepine) is available on the PBS for both treatment and prevention of bipolar disorder. The sedative effects of this medication make its impact very useful in over-active patients and in those with insomnia. Patients who are hypomanic, and especially patients who are severely ill, can often require much higher doses of medication, especially at night. As the patient becomes sedated, after control of the symptoms has been achieved, it is often possible to titrate the dose of medication downwards progressively, until a maintenance dose of Zyprexa which does not cause sedation has been achieved. Weight gain, with disturbance of lipid profiles and blood sugar levels are complications of Zyprexa, and should be monitored from time to time.
Seroquel (Quitiepine) is also a sedative agent, which is also indicated on the Australian PBS for treatment of bipolar illness. Similar advice about high initial doses, especially at night is applicable. In maintenance usage , weight gain and tiredness are fairly common problems.
Other anti-manic atypical agents include Risperdal (which tends to cause hypotension), Solian (which tends to cause marked elevation of prolactin levels with some later risk of osteoporosis), and Abilify (which has very little risk of weight gain , but more risk of restless legs and Parkinsonian side-effects) may also be used. However, these agents are less immediately sedative, and may make immediate management of a hypomanic patient more difficult and less predictable.
In some patients, benzodiazepines (particularly Clonazepam) may be adequately effective. Chlorpromazine (Largactil) is a traditionally effective older agent, predictably sedative but with more risk of Parkinsonian side-effects, and long term risk of tardive dyskinesia (chewing movements etc)..
Long-term care : Bipolar disorder is a permanent condition, and intense long-term biochemical control will lessen the morbidity (estimated at 40% of life years in those already diagnosed!). It is very useful if the patient and his/her family can accept that we are dealing with a permanent biochemical imbalance, and that maintenance mood stabilisers are intended to prevent and minimise any future episodes of illness. Various forms of CBT and supportive therapy are useful, but are likely to be ineffective without medication also.