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Akathisia is an often miserable side-effect of various anti-psychotic medications.  It includes a feeling of inner restlessness and an inability to sit still.  Patients will often shift from foot to foot.  Psychiatrists sometimes don't notice it even when it is obvious or don't take it seriously enough.

Usually, the best way to treat akathisia is to change to another anti-psychotic which causes less of this side-effect.  It can also sometimes be treated with medication, although very little quality research has been done of the issue.  All of the available studies are quite small.  

The most common medication strategy is to use propranolol, a beta-blocker medication most often used for high blood pressure.  It is also the best researched, but that isn't saying very much.  Benztropine, an anti-parkinsonian medication used to treat the extrapyramidal side-effects, might also help.  Three studies have reported some benefit with mirtazapine (Remeron), and single studies with cyproheptadine, pyridoxine (B-6), trazodone, nefazodone, mianserin, and clonazepam (Klonopin)

Akathisia Common, Interview Necessary: 40% get akathisia within 6 hours of haloperidol 5 mg. Ask patients if they feel restless, jittery, or unable to sit still. A few become more psychotic with increased hallucinations and bizarre caused by akathisia.  Akinesia was also a problem. Van Putten, UCLA, Arch Gen Psychiatry 84;41:;1036-40. Giving benztropine when not needed increases uncomfortable feelings and abnormal movement. Jonathan Cole, Harvard, Arch Gen Psychiatry 84;41:1030-4

Barnes Akathisia Scale: Akathisia is a syndrome of motor restlessness, usually caused by antipsychotic medication. Patients experience uneasiness and the urge to move with particular patterns of restless movement. This review focuses on the signs and symptoms of the condition, and its diagnosis and assessment using the 15 year old Barnes Akathisia Rating Scale. Its validity and reliability have been established, and it has been used extensively in clinical studies worldwide. The Barnes Akathisia Rating Scale--revisited. Barnes TR. London, UK. [email protected] J Psychopharmacol. 2003 Dec;17(4):365-70

Amantadine Loses Efficacy for Akathisia: 4 patients with neuroleptic akathisia treated amantadine were benefited at first but akathisia recurred and increased dosage only temporarily beneficial. One patient with EPS and akathisia had akathisia, but not EPS recur. Development of tolerance to the therapeutic effect of amantadine on akathisia. Zubenko GS, Barreira P, Lipinski JF Jr. J Clin Psychopharmacol 1984 Aug;4(4):218-20

Benztropine Might Help: In a DB PC crossover trial of just 6 patients with akathisia, IV benztropine 2 mg helped somewhat, but not propranolol 1 mg. Intravenous benztropine and propranolol challenges in acute neuroleptic-induced akathisia. Sachdev P, Loneragan C. Sydney, Australia. Clin Neuropharmacol. 1993 Aug;16(4):324-31. Ed: Other than suggest that benztropine might help, I don't think this study means anything. Benztropine can cause mental confusion.

Beta-Blockers Helped Some: In a 19-patient DB PC crossover study of propranolol (20 or 40 mg/day) or betaxolol (10 or 20 mg/day) or placebo period, there was no significant difference in the antiakathisia effects of propranolol and betaxolol. Randomized, double-blind, crossover, placebo-controlled comparison of propranolol and betaxolol in the treatment of neuroleptic-induced akathisia. Dumon JP, Catteau J, Lanvin F, Dupuis BA. University of Lille, France. Am J Psychiatry. 1992 May;149(5):647-50

Beta-Blocker: Propranolol Didn't Help Akathisia in Very Small Study: In a very small 11-patient 48-hour crossover DB PC study, propranolol didn't help akathisia. Propranolol as a primary treatment of neuroleptic-induced akathisia. Irwin M, Sullivan G, Van Putten T. VAMC, San Diego. Hillside J Clin Psychiatry. 1988;10(2):244-50

Beta-Blockers: Propranolol Did Help Akathisia in Very Small Study: In a very small 12-patient crossover DB PC 7-day study, propranolol 120 mg/day did reduce akathisia. Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study. Kramer MS, Gorkin R, DiJohnson C. Coatesville VA. Hillside J Clin Psychiatry. 1989;11(2):107-19

Beta-Blocker: Nadolol Didn't Help Akathisia: In a DB PC trial of 20 patients, those on nadolol 40-80 mg/day had no improvement in akathisia in a 19 day study.  A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia. Wells BG, Cold JA, Marken PA, Brown CS, Chu CC, Johnson RP, Nasdahl CS, Ayubi MA, Knott DH, Arheart KL. University of Tennessee. J Clin Psychiatry. 1991 Jun;52(6):255-60

Beta-Blocker: Metoprolol, a Beta-1 Blocker, Appears to Work: 9 pt rx 25-100/d. 7 helped akathisia. Later switched to propranolol without change. Selective beta-1. Efficacy of low-dose metoprolol in neuroleptic-induced akathisia. Kim A, Adler L, Angrist B, Rotrosen J. J Clin Psychopharmacol 1989 Aug;9(4):294-6

Beta-Blocker: Beta-2 Also Helped: Very small DB with experimental beta-2 blocker. 5 of 6 on med vs. 1 of 4 on placebo better. Effects of a specific beta 2-receptor blocker in neuroleptic-induced akathisia. Adler L, Duncan E, Angrist B, Hemdal P, Rotrosen J, Slotnick V. Psychiatry Res 1989 Jan;27(1):1-4

Clonazepam Might Help: In a 2-week, 12-patient DB PC study, clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). The clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia. Pujalte D, Bottai T, Hue B, Alric R, Pouget R, Blayac JP, Petit P. Montpellier, France. Clin Neuropharmacol. 1994 Jun;17(3):236-42

Cyproheptadine, Propranolol Helped in Very Short Study: In a 30-patient DB PC trial of cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, akathisia decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity. Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study. Fischel T, Hermesh H, Aizenberg D, Zemishlany Z, Munitz H, Benjamini Y, Weizman A. Rabin Medical Center, Israel. J Clin Psychopharmacol. 2001 Dec;21(6):612-5. Cyproheptidine costs $40/month vs. $4 for propranolol.

Mianserin Helped in Short, Small Study: In a 5-day 30-patient DB PC study, the 5-HT2 antagonist anti-depressant, mianserin (available from Europe) at 15 mg/day showed a significant reduction in all four akathisia subscales by Day 5 with mean reductions in the BARS global score of 9.9% with placebo and 52.2% with mianserin (P = 0.006).  Treatment of neuroleptic-induced akathisia with the 5-HT2 antagonist mianserin. Double-blind, placebo-controlled study. Poyurovsky M, Shardorodsky M, Fuchs C, Schneidman M, Weizman A. Israel. Br J Psychiatry. 1999 Mar;174:238-42

Mirtazapine as Good as Propranolol: Mirtazapine 15 jmg/d, an anti-depressant with marked 5-HT(2A) antagonism, did slightly better than propranolol 80 mg/d in a 7-day DB PC study of 90 antipsychotic-treated patients with akathesia. Both reduced AIA severity (-34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023). Five (16.7%) of 30 propranolol patients and none of mirtazapine discontinued due to hypotension or bradycardia. However, 7 mirtazepine vs 8 propranolol discontinued in all. Low-Dose Mirtazapine: A New Option in the Treatment of Antipsychotic-Induced Akathisia. A Randomized, Double-Blind, Placebo- and Propranolol-Controlled Trial. Poyurovsky M et al. Biol Psychiatry 2006 Feb 20.

Mirtazapine (Remeron) Helped: The nonselective serotonin (5-HT)-2A antagonists ritanserin, mianserin, and cyproheptadine have been found effective in neuroleptic-induced akathisia. Mirtazapine is similar to mianserin. In a 26 patient DB PC 5-day study, mirtazapine 15 mg/d did significantly better. Significantly more mirtazapine-than placebo-treated patients (53.8% [7/13] vs. 7.7% [1/13], p = 0.004) met response criterion. Mirtazapine was associated with modest improvement of psychotic and parkinsonian symptoms. Mild sedation was the only side effect. The role of mirtazapine in the treatment of akathisia induced by atypical antipsychotic agents merits further investigation. Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study. Poyurovsky M, Epshtein S, Fuchs C, Schneidman M, Weizman R, Weizman A. Israel. J Clin Psychopharmacol. 2003 Jun;23(3):305-8. Ed: Mirtazapine is somewhat expensive and often causes weight gain. Similar: Ann Pharmacother 2006 Mar 28.

Nefazodone Helped EPS, But Not Akathisia: Nefazodone, a relative of trazodone, blocks postsynaptic 5HT2A receptors and weakly inhibits serotonin reuptake. In a DB PC study of 49 patients on haloperidol 10 mg/d who developed EPS, nefazodone significantly reduced EPS as measured by both the Simpson Angus scale and CGI (p=0.007 and 0.0247) but akathisia and tardive dyskinesia did not differ between the two groups (p=0.601 and p=0.507). Efficacy of nefazodone in the treatment of neuroleptic induced extrapyramidal side effects: a double-blind randomised parallel group placebo-controlled trial. Wynchank D, Berk M. Witwatersrand University. Hum Psychopharmacol. 2003 Jun;18(4):271-5

Propranolol, Benztropine Appear to Help Akathisia in Very Small Study: In a 28-patient DB PC study of akathisia comparing propranolol (80 mg/day), benztropine (6 mg/day), and placebo, both propranolol and benztropine significantly improved akathisia by Day 3-5 of treatment while the placebo had no significant effects. Three patients developed confusion or forgetfulness by Day 3 of benztropine which cleared upon discontinuation of benztropine. A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis. Adler LA, Peselow E, Rosenthal M, Angrist B. New York VA. Psychopharmacol Bull. 1993;29(2):283-6

Trazodone Might Help: In a very poor quality uncontrolled study, nine female patients with akathisia were given trazodone up to 100 mg/day for 5 days. The authors report that patients demonstrated marked improvement of the akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone. Stryjer R, Strous RD, Bar F, Poyurovsky M, Weizman A, Kotler M. Beer Yaakov, Israel. Clin Neuropharmacol. 2003 May-Jun;26(3):137-41

Vitamin B-6 and Mianserin Both Helped: In a 5-day DB PC study of 60 schizophrenia and schizoaffective inpatients who have akathesia, vitamin B6 1200 mg/d  and mianserin 15 mg/d were each much better than placebo. Compared with the placebo group, the vitamin B6-treated and mianserin-treated patients showed a significant improvement in the subjective (P < 0.0001), subjective distress (P < 0.0001), and global (P < 0.0001) subscales. The objective subscale did not show significant positive results (P = 0.056), but there was a trend toward symptom amelioration in both groups. A reduction of at least 2 points on the Barnes Akathisia Rating Scale global subscale was noted in the vitamin B6 group (13/23, 56%) as well as in the mianserin groups (13/20, 65%), and in only one patient in the placebo group (1/17, 6%; P < 0.0005). Vitamin B6 Versus Mianserin and Placebo in Acute Neuroleptic-induced Akathisia: A Randomized, Double-blind, Controlled Study. Miodownik C, et al. Ben-Gurion University of the Negev, Israel. Clin Neuropharm 2006 March/April;29(2):68-72. Ed: This dose of B-6 is well into the toxic range if continued for an extended period.  Mianserin is available in Europe.