James E. Mack

Neurotoxic Syndrome Associated with Risperidone and Fluvoxamine

OBJECTIVE: To report a case of a neurotoxic syndrome in a patient undergoing concomitant treatment with risperidone and fluvoxamine. CASE REPORT: A 24-year-old African American woman hospitalized for psychosis was unresponsive to risperidone. Because of obsessive symptoms, low doses of fluvoxamine were added to her treatment regimen. Within 2 days, she developed confusion, diaphoresis, diarrhea, hyperreflexia, and myoclonus, which then progressed to rigidity, fever, and unresponsiveness, requiring endotracheal intubation. Symptoms resolved over 10 days with discontinuation of medication, hydration, and bromocriptine 5 mg 3 × daily. Ultimately, she was treated with olanzapine and fluvoxamine without adverse effects. DISCUSSION: This represents the first reported case of a neurotoxic syndrome secondary to treatment with risperidone and fluvoxamine. Differential diagnosis between neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) could not be accurately determined because of the overlap of signs and symptoms of both syndromes. NMS and SS may represent different aspects of a more generalized neurotoxic syndrome. This could be an important consideration in formulating treatment for neurotoxic syndromes. CONCLUSIONS: Clinicians should be aware of potentially serious adverse reactions that may occur during concomitant treatment with antipsychotics and selective serotonin-reuptake inhibitors.

Carisoprodol Withdrawal Syndrome

A 43‐year‐old man with chronic back and shoulder pain was treated with hydrocodone. He began taking excessive amounts of the drug, so his physicians stopped prescribing it. The patient then obtained the muscle relaxant carisoprodol on his own from several sources. He was consuming up to 30 or more tablets/day (≥ 10,500 mg/day) for several weeks, then abruptly stopped taking the drug. Within 48 hours he developed anxiety, tremors, muscle twitching, insomnia, auditory and visual hallucinations, and bizarre behavior. The symptoms intensified and peaked on the fourth day after carisoprodol cessation. The patient required brief treatment with olanzapine and tapering dosages of lorazepam while the symptoms gradually resolved. To our knowledge, this is the first documented case of a withdrawal syndrome with carisoprodol. The symptoms most likely resulted because of accumulation of meprobamate, the active metabolite of carisoprodol in humans. Clinicians prescribing carisoprodol should be aware of the possibility for abuse or addiction. Further, we recommend that carisoprodol be designated a controlled substance at the federal level.

Shock‐Like Sensations During Venlafaxine Withdrawal

Electric shock‐like sensations may occur after cessation of treatment with serotonin selective reuptake inhibitors but are reported in the literature only rarely with discontinuation of venlafaxine. Two patients experienced severe shock‐like sensations during venlafaxine withdrawal. For both patients symptoms occurred with lowering of the dosage and persisted for 5 days after complete discontinuation of the drug. These sensations may represent significant alteration of neuronal activity in the central nervous system.

Neuroleptic Malignant Syndrome during a Change from Haloperidol to Risperidone

OBJECTIVE: To report a case of neuroleptic malignant syndrome (NMS) in a patient whose therapy was being switched from haloperidol to risperidone. CASE REPORT: A 57-year-old African-American man, treated for schizophrenia with haloperidol for several years, developed NMS within 48 hours of the addition of low doses of risperidone and mirtazapine to his regimen. Symptoms, which included fever, generalized rigidity, and altered mental status, resolved after discontinuation of psychotropics, supportive management, and several weeks of treatment with bromocriptine and dantrolene. He was subsequently treated with olanzapine without adverse effects. DISCUSSION: Several cases of NMS have been reported with risperidone, but none under these circumstances. NMS most likely occurred in this patient as a result of the additive dopamine2 receptor blocking of haloperidol and risperidone. Sympathetic hyperactivity secondary to mirtazapine may also have been a contributing factor. If NMS may be induced by the simultaneous use of older, high-potency antipsychotics and newer, atypical antipsychotics such as risperidone, switching patients from older to newer antipsychotics may at × be difficult, since completely stopping one antipsychotic before starting the second may place patients at risk for psychotic relapse. CONCLUSIONS: Clinicians should closely monitor patients receiving both haloperidol and risperidone or combinations of similar medications.

Acute cardiovascular effects of methyl methacrylate monomer: characterization and modification by cholinergic blockade, adrenergic stimulation and calcium chloride infusion.

1. Methyl methacrylate monomer (MMA) given by i.v. infusion to anesthetized dogs caused a sustained hypotension, bradycardia, reduction of cardiac output and stroke volume, and increased peripheral resistance. 2. Epinephrine i.v. could reverse the hypotension but not the bradycardia; isoproterenol i.v. could reverse the bradycardia but not the hypotension. 3. Bilateral cervical vagotomy prevented bradycardia but not other cardiovascular effects of MMA, and prevented all respiratory effects except hypoxemia. 4. Calcium chloride i.v. reversed all circulatory changes except bradycardia; a combination of atropine and calcium reversed all cardiovascular changes from MMA.

Influence of veratridine on [3H]-l-quinuclidinyl benzilate ([3H]QNB) binding in mouse hindbrain

The neurotoxin veratridine is well known for its ability to open sodium channels in neuronal and muscle tissues in micromolar concentrations. It has also been shown that veratridine is an inhibitor of the potent muscarinic receptor antagonist L-quinuclidinyl benzilate (QNB) at these concentrations. These findings prompted us to examine the relationships between action potential sodium channels and muscarinic receptors in a glass-fiber filtration assay for [3H]QNB binding to mouse hindbrain membranes using agents known to affect interconversion of the affinity states in some muscarinic receptor populations, i.e. guanosine triphosphate (GTP) and magnesium (Mg2+). The actions of the sodium channel antagonist tetrodotoxin (TTX) were also examined. Veratridine inhibited [3H]QNB binding with a Ki value of approximately 2.5 microM. This inhibition exhibited a competitive mechanism at higher concentrations (5-10 microM), while showing an apparent non-competitive action at low concentrations (1 microM). Magnesium caused a parallel shift to the right in the inhibition curve with a 32% increase in the veratridine Ki. GTP caused a non-parallel shift to the left with the greatest displacement occurring at lower veratridine concentrations (2-5 microM). The addition of magnesium to GTP did not alter the action of GTP significantly. TTX (5 microM) caused a parallel shift of the veratridine inhibition curve to the right. In addition, TTX alone inhibited the binding of [3H]QNB. Therefore, it appears that there may be more than one binding site for veratridine which may be linked to the muscarinic system and that these may be action potential sodium channels.