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This combination of movement and psychiatric disorders is dif cult to treat, and one is faced with instituting an antidepressant regimen or perhaps using one of the newer class of antipsychotic medications that have the least extrapyramidal side effects (see below and Chap 50) While the selective serotonin reuptake inhibitors have been useful in cases of apathetic depression, they may cause slight worsening of parkinsonian symptoms In our hands, trazodone has been most helpful in treating depression and insomnia, the latter also being a major problem in some patients Excitement and aggressiveness appear in a few A return of libido may lead to sexual assertiveness Confusion and outright psychosis (hallucinations and delusions) are seen in advanced cases of Parkinson disease when high doses of L-dopa are required and the disease has been present for many years This may rst be treated by attempting to reduce the dose of the drug.

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If this is not tolerated, the atypical neuroleptics olanzapine, clozapine, risperidone, or quetiapine in low doses are recommended by Friedman and Lannon The side effects of these drugs include sleepiness, orthostatic hypotension, and sialorrhea As noted above, clozapine has been said to provide an additional bene t of suppressing dyskinesias in advanced Parkinson disease (Bennett et al), but it requires surveillance of the white blood cell count because of the idiosyncratic occurrence of agranulocytosis in up to 2 percent of patients Although useful in the treatment of frankly psychotic patients, these drugs tend to be far less effective once dementia has supervened The anticonvulsant valproate is also said to be useful in this circumstance, but in our hands it has not been as effective as clozapine and related drugs.

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Despite their lesser tendency to produce rigidity, olanzapine and probably the other similar agents in high doses may slightly worsen motor disability An important note of warning: anticholinergic agents or Ldopa should not be discontinued abruptly in advanced Parkinson disease If this is done, the patient may become totally immobilized by a sudden and severe increase of tremor and rigidity; rarely, a neuroleptic syndrome, sometimes fatal, has been induced by such withdrawal Reducing the medication dose over a week or so is usually adequate With progressive loss of nigral cells, there is an increasing inability to store L-dopa and periods of drug effectiveness become shorter In some instances, the patient becomes so sensitive to L-dopa that as slight an excess as 50 to 100 mg will precipitate choreoathetosis; if the dose is lowered by the same amount, the patient may develop disabling rigidity.

Table 14-5.

With the end-of-dose loss of effectiveness and on-off phenomenon, which with time become increasingly frequent and unpredictable, the patient may experience pain, respiratory distress, akathisia, depression, anxiety, and even hallucinations Some patients function quite well in the morning and much less well in the afternoon, or vice versa In such cases, and for end-of-dose and on-off phenomena, one must titrate the.

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