Lithium neuroleptic drugs

Goldney RD, Spence ND. Safety of the combination of lithium and neuroleptic drugs. Am J Psychiatry 1986 143 882-884. 

It is not clear that so-called antipsychotic drugs are superior to other types of drugs with sedative effects but different mechanisms of action. Lithium, benzodiazepines and opium have been shown to be comparable to neuroleptics in the treatment of psychotic states in some studies. The ability of the neuroleptic drugs to reduce the most characteristic symptoms of psychosis such as hallucinations, delusions and thought disorder have often been interpreted as evidence of their specifically antipsychotic or antischizophrenic action (The National Institute of Mental Health Psychopharmacology Service Center Collaborative Study... 

A literature review of permanent neurological complications of acute lithium toxicity noted that a cerebellar syndrome is quite common and that neuroleptic drugs can worsen toxicity, as might rapid reduction of raised serum lithium concentrations (182). However, the latter point is speculative at best hemodialysis remains the treatment of choice for severe lithium poisoning. 

However, lithium can be associated with the neuroleptic malignant syndrome in patients who are taking neuroleptic drugs, as in the following cases ... 

The authors concluded that lithium alone can cause neuroleptic malignant syndrome, since no neuroleptic drugs had been co-administered in this case. 

Of 47 cases of drug-induced pancreatitis reported to the Danish Committee on Adverse Drug Reactions between 1968 and 1999, one involved lithium (plus a neuroleptic drug) (357). Whether lithium was causally involved is not known. 

There were no changes in lithium pharmacokinetics when risperidone was substituted open-label for another neuroleptic drug in 13 patients (634). On the other hand, an 81-year-old man had an acute dystonic reaction 4 days after lithium was added to a regimen of risperidone, valproic acid, and benzatropine (635). 

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. 

Several cases of neurotoxicity in patients taking lithium and thioridazine have been reported. The cause of this interaction has not been resolved, but lithium seems compatible with all neuroleptic drugs, although patients should be carefully monitored (726-728). 

Bupropion has about the same seizure potential as tricyclic antidepressants (SEDA-8, 30), but the manufacturers noted an increased risk of seizures in patients taking over 600 mg/day in combination with lithium or neuroleptic drugs (SEDA-10, 20). 

Neuroleptic drugs are often used in mood stabilizer combinations. However, there have been few controlled studies of the use of such combinations, and interactions are potentially dangerous. The advantages and disadvantages of all currently used mood stabilizer combinations have been extensively reviewed (641). Some effects are well known neurotoxicity, hypotension, somnambulistic-like events, and cardiac and respiratory arrest associated with the combination of lithium and traditional neuroleptic drugs considered as a first-line treatment for classic euphoric mania with psychotic features. 

The long-term toxic effects of lithium, such as nephrogenic diabetes insipidus, which has been calculated to occur in up to 5% of patients, and the rare possibility of lithium combined with neuroleptics being neurotoxic, has stimulated the research for other drug treatments. However, apart from the neuroleptics, these drugs have not been studied as extensively in the treatment of acute mania, but are worthy of consideration because of their reduced side effects. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

In CONCLUSION, lithium is universally accepted as a mood-stabilizing drug and an effective antimanic agent whose value is limited by its poor therapeutic index (i.e. its therapeutic to toxicity ratio). Neuroleptics are effective in attenuating the symptoms of acute mania but they too have serious adverse side effects. High potency typical neuroleptics appear to increase the likelihood of tardive dyskinesia. Of the less well-established treatments, carbamazepine would appear to have a role, particularly in the more advanced stages of the illness when lithium is less effective. 

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