Neurological effects lithium

Seizures and other neurological effects have been described in a few cases when lithium was added to clozapine (626), but in other instances the combination was beneficial in overcoming treatment resistance or attenuating clozapine-induced leukopenia. Five treatment-resistant patients were treated successfully with a combination of clozapine and lithium with no clinically significant adverse events (627). However, a 59-year-old woman developed neurotoxic symptoms 3 days after lithium was added to clozapine the symptoms resolved when both drugs were stopped and recurred with rechallenge (628). 

Seizures and other neurological effects have been described in a few cases when lithium was added to clozapine (204), but in other instances the combination was beneficial in overcoming treatment resistance or attenuating clozapine-induced leukopenia. 

MnHiple sclerosis Lithium was effective in a mouse model of experimental autoimmune encephalomyelitis (a model of multiple sclerosis). It reduced neurological symptoms if administered both before and after induction of the illness ami the animals rapidly relapsed if lithium was withdrawn [34 ]. 

Aggravation of the extrapyramidal effects of antipsychotic agents have been described and it has been reported that the use of lithium in combination with haloperidol may result in irreversible neurological toxicity. Lithium can increase the hypothyroid effects of antithyroid agents or iodides. 

Kahn NH, Shelton SJ Defensive behaviors in infant rhesus monkeys environmental cues and neurochemical regulation. Science 243 1718-1721, 1989 Kahnowsky LB, Kennedy F Observations in electric shock therapy apphed to problems of epilepsy. J Nerv Ment Dis 98 56-67, 1943 Kampen D, Sherwin B Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol 83 979-983, 1994 Kane JM, Quitkin FM, Rifkin A, et al Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar 11 illness a prospective placebo-controlled comparison. Arch Gen Psychiatry 39 1065-1069, 1982 Kaneno S, Komatsu H, Fukamauchi F, et al Biochemical basis of antidepressant-effect of low dose of sulpiride. Japanese Journal of Psychiatry and Neurology 45 131-132, 1991... 

Tremor is one of the most common adverse effects of lithium treatment, and it occurs with therapeutic doses. Propranolol and atenolol, which have been reported to be effective in essential tremor, also alleviate lithium-induced tremor. Other reported neurologic abnormalities include choreoathetosis, motor hyperactivity, ataxia, dysarthria, and aphasia. Psychiatric disturbances at toxic concentrations are generally marked by mental confusion and... 

Neurologic adverse effects of lithium include reduced reactivity, lack of spontaneity, intellectual insufficiency, memory problems, difficulty in concentration, dysphoria. Some of these effects may be related to the therapeutic action of lithium in reducing hypomania. However, hypothyroidism, weakness and fatigue due to hypercalcemia, and breakthrough depression must be considered in the presence of these symptoms. 

In keeping with this medication spellbinding effect, normal volunteers on small doses suffer impairments of their reflexes but do not realize or acknowledge the impairment (Linnoila et al., 1974). Lithium patients who report no side effects often have grossly obvious tremors. The failure of patients on maintenance therapy to notice their own neurologic defects clearly demonstrates that long-term treatment with lithium is medication spellbinding. 

Concurrent use of lithium may be a risk factor for neurological adverse effects. 

Erythrocyte/plasma lithium concentration ratios were lower in patients taking phenothiazines or haloperidol than in those taking lithium alone (620,621), and the former group had a higher incidence of neurological and renal adverse effects (621). 

In a 6-week open study of risperidone (mean dosage 4.7 mg/day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3% were completely symptom-free (35). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n = 13), exacerbation of mania ( n = 5), drowsiness (n = 3), and impotence (n = 2). 

Typical symptoms of lithium intoxication are summarized in Table 2 [122-127]. The clinical picture of hthium intoxication is dominated by neuromuscular and cerebral symptoms in mild cases apathy, muscle weakness, tremor, and unsteady gait are seen. In more severe cases speech disturbances, myoclonic twitching, coma and convulsion can occur. Pulse irregularities and circulatory collapse may supervene. Lithium often causes T-wave flattening or inversion on the electrocardiogram, but clinically important cardiovascular effects are rare, with sinus-node dysfunction reported most often [123]. Residual neurological sequelae consisting of cerebellar dysfunction with ataxia, neuropathy and supra-bulbar symptoms are not unusual. 

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