Early after stroke, anterior left-sided lesions involving the cortex and subcortical regions, especially the basal ganglia, and right posterior lesions are more frequently associated with depression.⁽²⁾ In time these associations become less marked.⁽³⁾ Cognitive impairment is closely associated with depression early after stroke,⁽⁴⁾ and is present in 70 per cent of those with major and 43 per cent of those with minor depression. Old age, a past or family history of depression, and negative life events in the preceding 6 months substantially increase the incidence of post-stroke depression.

Disruption of fronto-subcortical circuits, directly or as a distant effect of stroke, plays a central role in the causation of depression. Decreased metabolism in orbitofrontal, anterior cingulate, and inferior temporal regions has been reported using PET.⁽⁵⁾ Serotonergic mechanisms have been implicated, with a reduction of 5-hydroxytryptamine-2 receptor binding in the temporal cortex, especially in left hemisphere stroke.

The average duration of major depression is around 1 year, with spontaneous remission in many patients. Symptoms of minor depression may persist for 2 years or more. The presence of depression and other psychiatric diagnosis in the first 3 years after a stroke substantially increases the risk of death after controlling for cardiovascular and other risk factors.

Anxiety in the acute post-stroke phase is associated with high mortality rates, comparable to those in depressed patients.

Studies using PET have suggested that depression and anxiety in Parkinson’s disease are associated with a specific loss of dopamine and noradrenaline innervation in the limbic system.⁽¹²⁾ Post-mortem studies have also described loss of dopaminergic neurones in the ventral tegmental area.⁽¹³⁾ Degeneration of these neurones leads to dysfunction of the orbitofrontal cortex with secondary effects on the serotonergic cell bodies of the dorsal raphe.⁽⁵⁾

Optimal control of neurological symptoms may lead to improvement in depression and should be a management aim. Repeated assessment may be needed to differentiate features of the disease, such as apathy, from the symptoms of depression.

There are few studies describing the treatment of depression in Parkinson’s disease. When antidepressants are clinically indicated because of the severity or persistence of symptoms, the antidepressant profile of side-effects should be considered. Antidepressants with strong anticholinergic effects, such as amitriptyline, may increase cognitive impairment and SSRIs may be preferable. Electroconvulsive treatment is also effective for Parkinson’s disease patients with depression and may also transiently improve motor symptoms.

Psychotic symptoms may represent intrusion of REM sleep imagery into wakefulness. They may be more frequent in those receiving anticholinergics and dopamine agonists, but there is no clear association with dosage or duration of treatment. Stimulation of hypersensitive dopaminergic receptors in the nigrostriatal system by dopaminergic drugs may explain psychosis early in the disease, but it is unlikely to explain late psychosis. The therapeutic efficacy of atypical neuroleptics suggests a role for mesolimbic dopaminergic and serotonergic pathways. Cholinergic deficiency may also be relevant, in patients with dementia and atrophy of the nucleus basalis.

In patients with clouded consciousness, infection, cerebrovascular accidents, and other relevant pathologies need to be excluded. Revision of dopaminergic medication should come next, with reduction of polypharmacy and dose tapering. Anticholinergics, selegiline, amantadine, and dopamine agonists may need to be discontinued, as they are more likely to trigger psychosis.

In most patients antipsychotic drugs are needed, as dopaminergic medication is needed to preserve acceptable motor function. Atypical neuroleptics such as clozapine, with its low D2 receptor affinity and few extrapyramidal side-effects, are preferable to typical neuroleptics. Clozapine is effective at doses of less than 100 mg per day. Initial recommended doses of 6.25 to 12.5 mg daily should be gradually increased until the symptoms are controlled. The danger of agranulocytosis and the need to monitor the blood picture
are the main drawbacks, and other atypical neuroleptics (particularly quietiapine) may be preferable. Cholinesterase inhibitors may also be helpful in treating psychotic symptoms in patients with cognitive impairment.