Neuroleptic Malignant Syndrome causes

Severe and Potentially Irreversible Neurological Syndromes (Tardive Dyskinesia and Neuroleptic Malignant Syndrome) Caused by Neuroleptics... 

Burke RE, Fahn S, Mayeux R, Weinberg H, Louis K, Willner JH. Neuroleptic malignant syndrome caused by... 

Nielsen J, Bruhn AM. Atypical neuroleptic malignant syndrome caused by olanzapine. Acta Psychiatr Scand. 2005 112 238-40. 

Neuroleptic malignant syndrome is an acute iatrogenic condition caused by neuroleptics, characterized by tremor, catatonia, fluctuating consciousness, hyperthermia, and cardiovascular instability. It is relatively uncommon, occuring in 1-1.5% of patients but is fatal in 11-38%, most often due to cardiovascular collapse (Jahan et al. 1992). The pathogenesis of neuroleptic malignant syndrome is poorly understood, but it is believed to result from altered dopamine and serotonin transmission in the hypothalamus, spinal cord, and striatum. Treatment includes discontinuation of neuroleptics and administration of drugs that increase dopamine transmission bromocriptine or L-dopa (Jahan etal. 1992 Baldessarini 1996). 

Geriatric Considerations - Summary Pramipexole is a nonergot dopamine agonist that directly stimulates dopamine Dj receptors. It can be used in combination wit h le-vodopa or as monotherapy. If discontinued, pramipexole should be slowly tapered because abrupt discontinuation can cause confusion, hallucinations, and a condition similar to neuroleptic malignant syndrome. 

The diagnosis of GHB withdrawal may be difficult because it is similar to sedative or alcohol withdrawal syndromes, as well as to withdrawal from sympathomimetic agents such as cocaine, methamphetamine, and ecstasy. GHB withdrawal may also be confused with serotonin syndrome (a reaction caused by a combination of drugs, one of which increases serotonin levels in the body, such as Prozac) and neuroleptic malignant syndrome (a rare reaction to an antiseizure medication). 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian-like movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability (see Chapter 29 Antipsychotic Agents Lithium). 

Risperdal was first marketed in 1994 as an atypical neuroleptic. The clinical trials, most of which lasted a few weeks, were too short to determine the rate of tardive dyskinesia and many other adverse effects. Indeed, the brief controlled clinical trials used for the approval of both clozapine and risperidone do not provide sufficient information to determine either efficacy or safety since the drugs would be used for months and years in individual patients, rather than for a few weeks (see chapter 13). Patients taking the medications over the coming years will provide the experimental data. However, since Risperdal is a potent dopamine blocker, it should have been anticipated that it would cause similar adverse reactions as the older neuroleptics. In my own experience, I have evaluated many cases of tardive dyskinesia caused by Risperdal, Zyprexa, and Geodon. Meanwhile, the Food and Drug Administration (FDA) has required the same tardive dyskinesia and neuroleptic malignant syndrome warnings on the labels of clozapine and risperidone as on the labels of the older neuroleptics. 

Risperdal causes all the extrapyramidal reactions found with other neuroleptics, including tardive dyskinesia (Addington et al., 1995) and neuroleptic malignant syndrome (Mahendra, 1995 Singer et al., 1995 see chapter 4). It is too early to tell if the rate of tardive dyskinesia will differ from that of other neuroleptics. 

SSRIs can cause most of the neurological disorders associated with the neuroleptic drugs, including a serotonergic syndrome that resembles neuroleptic malignant syndrome. The similar result is probably due to the capacity of SSRIs to impact the dopaminergic system. Recent studies (e.g., Miura et ah, 2007) continue to confirm the early clinical suspicion that SSRIs were not quite as selective as their name implies and in fact impinge on other neurotransmitter systems. 

Weller, M., Kornhuber, J. (1993). Does clozapine cause neuroleptic malignant syndrome American Journal of Psychiatry, 54, 70-71. 

Whether lithium alone can cause neuroleptic malignant syndrome is controversial (SEDA-23, 24). 

Although the neuroleptic malignant syndrome has been reported in patients taking these atypical neuroleptic drugs, it is less common than in patients taking typical neuroleptic drugs, and lithium may have increased the risk in these cases. Co-administration of lithium and risperidone has been associated with the rabbit syndrome (638), but this reaction was probably caused by the risperidone, and the role of lithium was not clear. 

The authors of the last report pointed out that such atypical cases may support either a spectrum concept of neuroleptic malignant syndrome or the theory that neuroleptic malignant syndrome secondary to atypical neuroleptic drugs differs from that caused by conventional neuroleptic drugs. They suggested that more flexible diagnostic criteria than currently mandated in DSM-IV may be warranted. 

Although quetiapine seems to cause a lower incidence of extrapyramidal symptoms, a case of neuroleptic malignant syndrome has been described (9). 

Concomitant administration of quetiapine and fluvoxamine reportedly caused neuroleptic malignant syndrome (18). 

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