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Their use cannot be justified for trivial illnesses but they may be used for life-threatening conditions when the benefits outweigh the risks. Drugs with a TR of one or less cannot be used therapeutically. A type A adverse drug reaction is a possibility if a patient is given a higher than recommended dose for any particular route of administration due to practitioner error. In order to avoid this it is good clinical practice for drug dosages to be checked by another member of staff prior to administration. Where this is not possible, or impracticable, extreme care must be taken to ensure that a patient receives the right dose of the correct medicine by the route intended.

Bipolar depression tends to run in families, so there may be a genetic element to its aetiology. First-degree relatives of patients with bipolar depression are more likely to develop mood disorders than relatives of those who do not have bipolar depression. Twin studies have shown concordance rates for bipolar depression of more than twins. Bipolar depression appears to be a complex genetic illness, with susceptible genes interacting with environmental factors and adverse life events. Both depression and mania are associated with changes in brain monoamines. It was observed that the antihistamine imipramine and the anti-tuberculosis drug iproniazid had antidepressant activities.

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