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Dopaminergic side effects

Dopaminergic side effects

While dopamine D2 blockade in the meso-limbic pathway produces the desired symptom relief, three other pathways, the meso-cortical, nigro-striatal and tuberoinfundibular, all use D2 receptors and are also blockaded. This leads to a series of side effects dependent on the function of each pathway. Meso-cortical blockade has been implicated in the exacerbation of cognitive impairment and negative symptoms.

It is thought that the meso-cortical pathway may already have lowered dopaminergic activity in those suffering from schizophrenia, and treatment serves to compound this problem. Nigro-striatal blockade leads to a range of movement disorders, including dystonias, pseudo-parkinsonian symptoms, akathisia and tardive dsykinesia. These are referred to as extrapyramidal side effects (EPSE). These are often found to be the most distressing and debilitating symptoms among people taking the drug and have been identifi ed as one of the causes of non-concordance. Acute dystonic reactions, such as an oculogyric crisis, where the eyes roll back in the head, or torticollis, where there is contraction of the neck muscles, are due to muscle spasm and can be life-threatening. Treatment is usually intra-muscular administration of an anticholinergic, which provides rapid relief. Younger, treatment-naïve people are more likely to develop an acute dystonic reaction. Pseudo-parkinsonism (tremor, rigidity, bradykinesia and bradyphenia) can also be alleviated by the use of anticholinergics, reduction in dose or use of an atypical antipsychotic. This is due to the reciprocal nature of dopamine and acetylcholine in the nigro-striatal pathway. Dopamine antagonism produces a relative excess of cholinergic activity.

By inhibiting cholinergic activity the ratio between dopaminergic and cholinergic activity is restored to some extent, thus reducing the side effects. Another distressing side effect in this group is akathesia, a subjective sense of inner restlessness. It is associated with irritability from a behavioural perspective and in extreme, aggression and suicide. There is debate regarding treatment effi cacy for akathesia with anticholinergics favoured in the UK and low-dose propanalol in the USA, although there appears little to choose between them . A debilitating and irreversible movement disorder associated with long-term treatment is tardive dyskinesia (TD).

It is characterised by facial contortions, particularly of the mouth and tongue, and uncontrolled limb movements. Its cause remains rather unclear but appears to be a response to prolonged D2 antagonism in the nigro-striatal pathway whereby the receptors up-regulate or become supersensitive to combat the blockade, which leads to hyperactivity. Approximately 5% of people maintained on typical antipsychotics will develop TD every year .

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