Haloperidol mania

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Clozapine (Clozaril). Clozapine was introduced over 30 years ago but has only been available in the United States since 1990. It remains the medication of choice for treatment-resistant schizophrenia. Since its introduction, it has been used to treat acute mania with excellent results. Furthermore, it avoids the potential for tardive dyskinesia posed by haloperidol and the other typical antipsychotics. 

Antipsychotic drugs, such as flupentixol and haloperidol are the mainstay of treatment for acute attacks of mania. Lithium is not indicated as it may take a few days before the drug exerts an effect. Lithium may be given concomitantly with an antipsychotic drug. 

Other indications. Acutely, there is sedation with anxiolysis after neurolep-tization has been started. This effect can be utilized for psychosomatic uncoupling in disorders with a prominent psychogenic component neuroleptanalgesia (p. 216) by means of the buty-rophenone droperidol in combination with an opioid tranquilization of overexcited, agitated patients treatment of delirium tremens with haloperidol as well as the control of mania (see p. 234). 

For more than 40 years, Li+ has been used to treat mania. While it is relatively inert in individuals without a mood disorder, lithium carbonate is effective in 60 to 80% of all acute manic episodes within 5 to 21 days of beginning treatment. Because of its delayed onset of action in the manic patient, Li+ is often used in conjunction with low doses of high-potency anxiolytics (e.g., lo-razepam) and antipsychotics (e.g. haloperidol) to stabilize the behavior of the patient. Over time, increased therapeutic responses to Li+ allow for a gradual reduction in the amount of anxiolytic or neuroleptic required, so that eventually Li+ is the sole agent used to maintain control of the mood disturbance. 

Brown, D., Silverstone, T., and Cookson, J. (1989) Carbamazepine compared to haloperidol in acute mania. Int Clin Psychopharmacol 4 229-238. 

CMS = Global Mania Scale HAL = haloperidol HS = at night (for sleep) ... 

Brown AS, GershonS Dopamine and depression. J Neural Transm 91 75-109, 1993 Brown D, Silverstone T, Cookson J Carbamazepine compared to haloperidol in acute mania. Int Clin Psychopharmacol 4 229-238, 1989 Brown CM Endocrine aspects of psychosocial dwarfism, in Hormones, Behavior, and Psychopathology. Edited by Sachar E. New York, Raven, 1975 Brown GR, RundeU JR A prospective study of psychiatric aspects of early HIV disease in women. Gen Hosp Psychiatry 15 139-147, 1993 Brown GW, Harris TO Aetiology of anxiety and depressive disorders in an inner-city population, 1 early adversity. Psychol Med 23 143-154, 1993 Brown GW, Harris T, Copeland JR Depression and loss. Br J Psychiatry 130 1-18, 1977... 

Freeman TW, Clothier JL, Pazzaglia P, et al A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry 149 108-111,1992 Frenchman IB, Prince T Clinical experience with risperidone, haloperidol, and thioridazine for dementia-associated behavioral disturbances. Int Psychogeriatr 9 431-435, 1997... 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

Janicak et al. (87) studied the relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder. Sixty-two patients (29 depressed type, 33 bipolar type) entered a randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). They found no difference between risperidone and haloperidol in the amelioration of psychotic and manic symptoms nor any significant worsening of mania with either agent. For the total PANSS, risperidone produced a mean decrease of 16 points from baseline, compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively and for the CARS-M mania factor, 3 and 7 points, respectively. 

Lorazepam (2 mg i.m.) was found to be equivalent to haloperidol (5 mg i.m.) either alone or when added to ongoing antipsychotic treatment, and significantly reduced the likelihood of akathisia and dystonia (167). In the treatment of acute mania, lorazepam has also been reported useful as an adjunct to lithium, as well as antipsychotics (157, 163, 165, 168, 169). 

Limited evidence indicates that carbamazepine plus an antipsychotic may also benefit some schizophrenic patients. This is an interesting possibility in view of the similar antimanic properties of lithium and carbamazepine (375). This area requires further research, especially to clarify the indications for combining anticonvulsants with an antipsychotic. For example, mania complicated by psychotic features may benefit from lithium, valproate, or carbamazepine augmented by antipsychotics. Because carbamazepine induces the metabolism of at least some antipsychotics (e.g., haloperidol, thiothixene), dose adjustment based on TDM may be necessary to achieve the optimal effect. 

Verapamil Versus Other Psychotropics. Garza-Trevino et al. (258) conducted a 4-week, randomized, double-blind study comparing verapamil with lithium for acute mania and found no clinical or statistically significant differences between the two treatments. These results are difficult to interpret, however, because data about the amount and timing of rescue medication (i.e., haloperidol, lorazepam) were not presented. Further, more patients on verapamil required these agents. 

Dwight et al. (291) reported their experience with risperidone in eight patients with schizoaffective disorder (six bipolar type two depressive type). All six bipolar type patients showed the onset of or an increase in mania shortly after starting risperidone (mean number of treatment days = 7 3 mean dose = 7 1 mg/day). In this context, O Croinin et al. (292) reported on a chronic paranoid schizophrenic patient who was admitted in an acute psychotic state unresponsive to thioridazine or CPZ. Risperidone was started (6mg/day by day 3), but by the end of the first week she was displaying hypomanic symptoms. When risperidone was discontinued and haloperidol introduced, her hypomanic symptoms resolved. 

Sachs et al. (294) reported the results of a double-blind, randomized trial of acute mania. Patients were treated with risperidone, haloperidol, or placebo. 

Garfinkel PE, Stancer HC, Persad E. A comparison of haloperidol, lithium carbonate, and their combination in the treatment of mania. J Affect Disord 1980 2 279-288. 

Although mania in AIDS patients appears to be uncommon, such episodes can pose a serious hazard and require rapid control. Intravenous haloperidol or droperidol may be effective strategies, in part because this route of administration may be less likely than oral doses to induce acute extrapyramidal side effects ( 489, 490). Some concern, however, has been raised with the potential prolongation of the QT interval with droperidol, requiring caution in this regard. 

Haloperidol is used not only for mania, dementia and other psychotic conditions but can also be prescribed for Tourette s syndrome, a condition found in children and adults which is characterized by facial twitches, tics and uncontrolled shoulder and arm movements. As the the child gets older he/she may grunt, snort or shout obscenities without control. 

Juhl, R., Tsuang, M., Perry, P. (1977). Concomitant administration of haloperidol and lithium carbonate in acute mania. Diseases of the Nervous System, 38, 675-676. 

Cipriani A, Rendell JM, Geddes JR. Haloperidol alone or in combination in acute mania. Cochrane Database Syst Rev 2006 3 CD004362. 

Identical twin brothers, aged 37 years, had both suffered from bipolar disorder since their early twenties and had been treated with chlorpromazine, haloperidol, lithium, and carbamazepine before developing priapism. One of them developed priapism after taking trazodone 400 mg/day, and in the 2 years after the initial episode he suffered recurrent painless erections. Initially they occurred daily and lasted 4-5 hours. During a relapse of mania at age 37, he was given oral zuclopenthixol 40 mg/day. On the tenth day he presented with priapism of 4 days duration, which persisted despite zuclopenthixol withdrawal, needle aspiration, and phenylephrine instillation, but subsided 2 weeks later with conservative management. The... 

Similarly, risperidone caused extrapyramidal symptoms in fewer patients (24%) than haloperidol did (43%) in a two-phase study in patients with acute bipolar mania (phase I, 3 weeks, patients receiving either risperidone 1-6 mg/day, haloperidol 2-12 mg/day, or placebo (32). Plasma prolactin concentration was higher with risperidone (no data provided) prolactin-related adverse events included non-puerperal lactation, breast pain, dysmenorrhea, and reduced libido or sexual dysfunction these effects occurred in six patients on risperidone (4%) and in two on haloperidol (1.3%). 

Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F. Acute and continuation risperidone monotherapy in bipolar mania a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Eur Neuropsychopharmacol 2005 15 75-84. 

If haloperidol is used to treat mania, patients may experience a rapid switch to depression... 

When patients present in a manic episode, rapid remission of symptoms is required, particularly if the person is psychotic or experiencing severely disruptive behavior. In these cases, use of an antipsychotic medication is usual. These medications may include use of conventional or first generation antipsychotic medications, such as chloipromazine or haloperidol (Table 35.3). Recently, the second generation or atypical antipsycho tics have also shown efficacy in treatment of acute mania (American Psychiati ic Association, 2000). The latter agents are preferred due to their lower likelihood of inducing neuro-... 

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