Medicines for mental illness

Medicines for mental illness

Medicines are commonly prescribed for people with mental health problems. These comprise the medicines for the mental health problems and, with the greater recognition of associated physical illness, medicines for physical ill-ness. For those with severe mental health problems most will be prescribed mental health medicines for extended periods of time. This long-term, possi-bly lifelong, need means extended periods under the care of mental health professionals alone, jointly with shared care with a general practitioner (GP) or as discharged solely to the care of a GP. Many mental health medicines take weeks, if not months, to achieve a satisfactory response, although the short-term sedative effects may prove sufficient to allow early discharge of a still largely unwell person back into the community.

Most mental health medicines are associated with an array of side-effects that many patients find unpleasant and possibly unacceptable. In addition, many have only partial effectiveness or are only effective against some aspects of the illness. These factors make choice of medicine a key issue for pharma-cists and psychiatrists, with frequent trials of alternatives. This adds to the difficulty in determining the usefulness of the medicines, as assessments are often based on subjective responses and subject to a large number of variables.

The pivotal discoveries in the late 1940s and 1950s that changed mental health medicines were those of the phenothiazine antipsychotics, the tricyclic and monoamine oxidase inhibitor antidepressants and lithium for bipolar illness. Following shortly after was the arrival of the benzodiazepines both as sedatives and hypnotics. For the first time there was an array of medicines truly effective in managing psychosis, mania and depression.

The discovery of chlorpromazine is regarded as the key event that led to the fall in population of the asylums (then almost 150 000) but others claim that the decline had started earlier, following the changes to the 1959 Mental Health Act. Whichever explanation, the arrival in the 1970s of the long-acting formulations of antipsychotic drugs showed the development of community psychiatry was well under way.

Throughout the 1970s and 1980s there were few novel medicines in mental health, with most introductions being chemical variations or new formulations of those already available. Many were attempts to reduce the side-effects of the original drugs, make them work quicker or enhance their efficacy. However, the movement disorders (called extrapyramidal side-effects) associated with the antipsychotics and the toxicity of lithium and the antidepressants remained sources of concern. The 1990s saw another wave of developments as research into the mode of action of clozapine caused a change of attention of antipsychotic drug research to the mesolimbic system in the brain and to different receptors. Clozapine does not chronically alter striatal D₂ receptors but does appear to affect them. It also appears to have more effect on the limbic system and on serotonin (5HT₂) receptors, which may explain its reduced risk of extrapyramidal symptoms. The term ‘atypical’ is used to categorise those antipsychotic drugs that, like clozapine, rarely produce extrapyramidal side-effects.

Although the reason for the superiority of clozapine in schizophrenia treatment remains an enigma, a variety of theories have led to the develop-ment of a new family of antipsychotic drugs. Some mimic the impact of clozapine on a wide range of dopamine and serotonin receptors, for example olanzapine; others mimic the impact on particular receptors, for example 5HT₂/D₂ receptor antagonists such as risperidone; others focus on limited occupancy of D₂ receptors, for example quetiapine; while others focus on alternative theories such as partial agonism, for example aripiprazole.

The other revolution to occur in the 1990s was fluoxetine. Although not the first selective serotonin reuptake inhibitor, this antidepressant became the medicine for the masses in the 1990s and rivalled the 1960s’ use of the benzodiazepine diazepam in popularity. Throughout the 1990s and 2000s mental health practice saw a wide range of new medicines introduced for bipolar (antiepileptic drugs and antipsychotics), attention deficit hyperactiv-ity disorder (wider use of methylphenidate), Alzheimer’s disease (cholinester-ase inhibitors), schizophrenia (atypical antipsychotics) and depression (noradrenaline (norepinephrine) and serotonin reuptake inhibitors)