Ziprasidone (Geodon)

Ziprasidone appears to be an excellent atypical anti-psychotic.  It is definitely my favorite.  It is the least expensive and doesn't cause weight gain like olanzapine (Zyprexa), clozapine (Clozaril), or quetiapine (Seroquel).  It doesn't cause extra-pyramidal side-effects as often as risperidone (Risperdal).  It doesn't cause the excessive drowsiness of quetiapine (Seroquel).  Aripiprazole (Abilify) looks good but costs more.  It is very important to take Geodon with a meal or snack.  Otherwise, the blood level is cut in half and much of the benefit is lost.

Ziprasidone does cause a small increase in the heart's QTc interval.  Because of this, it is not to be used right after a heart attack or in someone suffering from uncontrolled heart failure.  Also, it should be avoided in patients with slow heart beats, those suffering from low potassium or low magnesium blood levels (usually from diarrhea or diuretics for blood pressure treatment), with congenital problems increasing the QT interval or with any of the following medications: dofetilide, sotalol, quinidine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, garifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, tacrolimus, or probucol.

Since 1) magnesium helps treat the torsade de pointe heart arrhythmia, 2) magnesium supplements have been proven to reduce the risk of arrhythmias, and 3) magnesium is a great supplement for everyone and very inexpensive, I recommend that my Geodon patients take magnesium 250 mg twice a day. Magnesium is a very valuable supplement, decreasing the risk of heart disease, diabetes, hypertension, and stroke.  The avoidance of Geodon by some psychiatrists seems unreasonable, especially since other traditional and atypicals have also been reported to increase the QTc interval with no evidence that Geodon causes more harm.

In placebo controlled trials, only 4% discontinued Geodon due to side-effects vs. 2% with placebo.  This is a very low level of side-effects compared to most other psychiatric medications.  Side-effects occurring at least 2% more often with ziprasidone than placebo are: sleepiness 7%, colds and upper respiratory infections 5%, extrapyramidal side-effects 4%, nausea 3%, dizziness 2%, dry mouth 2%, asthenia 2%, accidental injury 2%, nasal inflammation 2% and cough 2% (percentages all for amount more often than placebo).  The average weight gain was just 1 pound. 

Side-effects occurring just 1% more often than placebo: rapid heart beat, dizziness on standing, constipation, upset stomach, diarrhea, loss of appetite, muscle aches, restlessness, rash, fungal infection, and abnormal vision.  Others in the 1% category are abdominal pain, flu syndrome, fever, facial edema, chills, photosensitivity, flank pain, low temperature, high blood pressure, vomiting, agitation, tremor, hostility, tingling, confusion, high or low rate of movement, stumbling, and rigidity.

Ziprasidone is not affected much by other medications and doesn't have much affect on them.  Its blood level is 35% reduced by carbamazepine and 35% increased by ketoconazole.  In my experience, it is better to give Geodon near bedtime, since it often has a significant sleep effect.  Also, it is better to start with a lower dosage, such as 20-40 mg. once a day and increase the dosage after no significant side-effects are bothering the patient.

A benefit of ziprasidone that was discovered by a patient of mine is that the powder inside the Geodon capsule is tasteless.  It can be mixed with any liquid or food, e.g. jelly.  This is helpful for children who have difficulty swallowing or who object to medication, but need it.  Another oddity of Geodon is that all capsules cost the same amount of money.  This allows individuals having to pay for their own medications and taking less than 80 mg. at a time to purchase 80 mg. capsules, break open the capsule, divide the powder into roughly 40 mg. or 20 mg. piles, and make one 80 mg. capsule take the place of two 40 mg. capsules or four 20 mg. capsules.  This is a large cost savings: $130-$195 per month at Walgreen's prices as of 6/5/04.  Compared to other typicals available in the U.S., Geodon is the least expensive, especially with once a day dosing.  While it's half-life is only 7.5 hours, a number of other psychiatric medications with slightly shorter half-lives have been found equally effective in once a day dosing vs. multiple dosing.  While my personal experience is not a scientific study, my patients have done well on once a day dosing, although I would not exceed 80 mg. per dose.

Chlorpromazine (Thorazine) and Ziprasidone (Geodon) Did Equally Well: In a 12-week DB study of 306 patients with schizophrenia who had failed on three or more antipsychotics including 6-weeks of haloperidol just prior to the study, there was no overall difference between ziprasidone 80-160 mg/day and chlorpromazine 200-1200 mg/day.  Negative symptoms did improve more on ziprasidone, but improvements in BPRS total and core items and PANSS total scores were comparable at weeks 9 and 12. Ziprasidone was associated with a greater decrease in median prolactin levels and a lower incidence of clinically significant weight change. Neither agent caused any clinically important changes in QTc interval. Efficacy and tolerability of ziprasidone in patients with treatment-resistant schizophrenia. Kane JM, et al.  Albert Einstein College of Medicine and Pfizer. Int Clin Psychopharm 2006 Jan;21(1):21-28.

CATIE Trial Finds Ziprasidone Wanting: In the DB CATIE study of 444 schizophrenics who had discontinued the atypical antipsychotic randomly assigned during phase 1 and were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day; quetiapine, 200-800 mg/day; risperidone, 1.5-6.0 mg/day; or ziprasidone, 40-160 mg/day), the time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).

Haldol as Good as Geodon, but More EPS: In a 6-week, randomized study of ziprasidone (IM up to 3 days, then oral 40-80 mg, b.i.d.) or haloperidol (IM up to 3 days, then oral 5-20 mg/day) for 575 patients with acute exacerbation of schizophrenia. BPRS scores decreased more in the first three day IM phase for ziprasidone: -6.14 for ziprasidone vs. -4.13 for haloperidol, P<0.0018]. At 8 weeks, there were no significant between-group differences in BPRS scores. although BPRS negative subscale scores in favored ziprasidone. As expected, haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment had much more EPS and akathisia. Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study. Brook S, Walden J, et al. Krugersdorp, South Africa. Psychopharmacology (Berl). 2005 Jan 14

Haldol as Good as Ziprasidone: A DB 28-week study of ziprasidone 80-160 mg/d vs. haldol 5-15 mg/d in 301 patients found both were effective with ziprasidone superior for negative sypmtoms with fewer adverse events.  There was no change in body weight with either medicine. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. Hirsch SR, Kissling W, Bauml J, Power A, O'Connor R.. J Clin Psychiatry 2002 Jun;63(6):516-23: Imperial College of Medicine, London

Haldol 15 Equals Ziprasidone 160 mg./day: Another DB PC study of 4 mg, 10 mg, 40 mg and 160 mg/d ziprasidone found only 160mg/d equal to haldol 15/d. Benztropine use at any time during the study was much less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%).

Olanzapine (Zyprexa) and Ziprasidone Equal: In a 6-month DB flexible dosage continuation study of schizophrenic or schizoaffective patients who had responded, comparable improvements in BPRS and CGI severity scores were seen with both olanzapine and ziprasidone. Olanzapine increased weight, total cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Mean QTc values at endpoint were 407.1 msec (baseline mean=406.0 msec) and 394.4 msec (baseline mean=399.7 msec) for ziprasidone and olanzapine, respectively. No patient had a QTc interval >/=500 msec. Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Simpson GM, et al. University of Southern California. . Am J Psychiatry. 2005 Aug;162(8):1535-8.

Olanzapine (Zyprexa) and Ziprasidone Equal: In a DB multi-center study for 6-weeks for acute schizophrenic exacerbations, patients improved equally on both medications on all measures except for verbal fluency with favored olanzapine. Mt. Sinai Med School. Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Harvey PD, Siu CO, Romano S. Psychopharmacology (Berl). 2003 Nov 13

Olanzapine (Zyprexa) and Ziprasidone Equal but Side-Effects and Cost Favor Ziprasidone: In a 6-week DB study of 269 inpatients with schizophrenia or schizoaffective disorder, the mean daily doses were 130 mg for ziprasidone and 11.3 mg for olanzapine. Both antipsychotics were effective in improving symptoms. They did not differ significantly in primary or secondary efficacy measures (BPRS, CGI, PNSS, Depression). Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Simpson GM, Glick ID, Weiden PJ, Romano SJ, Siu CO. LAC + USC Medical Centers. Am J Psychiatry. 2004 Oct;161(10):1837-47. 

Perphenazine (Trilafon) Does Just as Well as Atypical Anti-Psychotics in Huge Study: In a huge 18-month DB PC study of 1493 patients with schizophrenia at 57 U.S. sites, patients received either olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the FDA. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine, while a little more effective, was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. Lieberman JA, et al. N Engl J Med. 2005 Sep 19

RisperidoneIn an 8-week DB study of 298 patients with acute schizophrenic or schizoaffective difficulties, ziprasidone 40 to 80 mg b.i.d. and risperidone 3 to 5 mg b.i.d were equal in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRS total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone caused higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and weight gain. Risperidone-treated patients averaged 7.4 mg/day vs. ziprasidone’s 114.2 mg/day. Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. Addington DE, Pantelis C, et al. Foothills Medical Center, Calgary, Alberta, Canada. J Clin Psychiatry. 2004 Dec;65(12):1624-33. At the dosages used, the risperidone would cost twice as much at U.S. prices.

Amisulpride and Ziprasidone Equal for Negative Schizophrenia: In a 12-week, DB study of 123 adults with predominantly negative-symptom schizophrenia, ziprasidone (40-80 mg b.i.d.) did as well as amisulpride (50-100 mg b.i.d.). Mean daily dose was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study. Olie JP, et al. University of Messina,  Italy & Pfizer Inc. Internat Clin Psychopharm 2006 May;21(3):143-151.

Dosage: High Dose Initially Best: In a study of 1096 Medicaid recipients with schizophrenia who had ziprasidone prescription, those with an initial dose: low (20-60 mg per day), and medium dose (61-119 mg)were more likely to relapse over the next year that those started out on high dose (120-160 mg) as measured using refill patterns, allowing 15-day gaps between expected refill dates (P=0.001). Other factors significantly associated with greater discontinuation of medication were monotherapy (versus combination therapy) and hospitalization within the 6 months prior to the index date of therapy. Being African-American was associated with greater discontinuation. Effect of initial ziprasidone dose on treatment persistence in schizophrenia. Mullins CD, et al. University of Maryland. Schiz Res 2006 Mar 15.

Dosage: Ziprasidone 40 mg./day Too Little in Acute Schizophrenia: In a study of 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder, patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia. Psychopharmacology (Berl) 1998 Nov;140(2):173-84

Dosage: Ziprasidone Maintenance 80 mg./day a Little Better than 40 mg/d: Stable, chronic schizophrenic inpatients were treated in a 1 year DB PC study of ziprasidone 40 mg/day (n = 72), 80 mg/day (n = 68), 160 mg/day (n = 67) or placebo (n = 71). The probability of relapse at 1 year was significantly lower in the ziprasidone 40, 80, and 160 mg/day groups (43%, 35% and 36%, respectively) compared to placebo (77%). Patients who remained on treatment for at least 6 months, only 9% subsequently relapsed on ziprasidone compared to 42% on placebo (P = 0.001). Discontinuation due to adverse events was similar with ziprasidone and placebo. Ziprasidone was indistinguishable from placebo in assessments of movement disorders, weight gain, or cardiovascular symptoms. A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg./day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. Arato M, O'Connor R, Meltzer HY; ZEUS Study Group. Int Clin Psychopharmacol. 2002 Sep;17(5):207-15; While chlorpromazine causes some weight gain, haloperidol caused none in one ziprasidone 6 month study.

Dosage: Ziprasidone 20mg. IM Better than 10mg. IM which is Better than 2mg. IM: 2 DB PC studies have shown that 10 or 20 mg of ziprasidone by injection is fast acting and superior to 2 mg. J Clin Psychiatry 2001 Jan;62(1):12-8. Ziprasidone causes more pain at the injection site than haloperidol (RR 5.5). Ziprasidone was well tolerated when given by IM injection at doses up to 80 mg daily. The most common adverse events with the 10-mg and 20-mg doses were nausea, headache, and dizziness. Per the package insert, the recommended dose is 10 to 20 mg. administered as required, up to a maximum dose of 40 mg. daily. A dose of 10 mg may be administered every 2 hours; a dose of 20 mg. of ziprasidone may be given every 4 hours. In practice, the 20-mg dose is more completely and more rapidly effective than the 10 mg. dose. A total of 90% of the subjects receiving 20 mg. were considered responders, vs. 57% of the subjects receiving 10 mg.

Metabolized by Aldehyde Oxidase: Two-thirds is metabolized by aldehyde oxidase (AO) and one-third by CYP3A4. There are no polymorphisms of the gene for AO. Therefore, humans all metabolize ziprasidone in the same fashion. Inhibitors of the metabolism of other medicines have no clinical effect on ziprasidone metabolism. Ziprasidone Metabolism, Aldehyde Oxidase, and Clinical Implications. Beedham C, Miceli JJ, Obach RS. J Clin Psychopharmacol. 2003 Jun;23(3):229-232 

Switch to Ziprasidone (Geodon) Easy: A random assignment, open study of 270 patients on traditional anti-psychotics, or olanzapine, or risperidone were tested with three different switching strategies.  All were found successful without significant difficulties. Patients reportedly improved. Doses used were 40-160 mg/d. Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia. Weiden PJ, Simpson GM, Potkin SG, O'Sullivan RL. J Clin Psychiatry. 2003 May;64(5):580-8

Ziprasidone, Molindone Least Weight Gain: In studies concerning body weight gain in a MEDLINE search from 1966 to March 2000, patients treated with olanzapine (Zyprexa) (average bodyweight gain 2.3 kg/month), clozapine (Clozaril) (1.7 kg/month), and quetiapine (Seroquel) (1.8 kg/month). Risperidone had an average bodyweight gain 1.0 kg/month and ziprasidone 0.8 kg/month. Body weight gain occurred most frequently in the first 12 weeks of treatment, so patients do not keep gaining the above weight indefinitely. Patients underweight at the beginning of treatment are at highest risk of gaining. The relative receptor affinities of the atypical antipsychotics for histamine H1 receptors as well as the ratio of their affinity for serotonin 5-HT2 and dopamine D2 receptors appear to be the most robust correlate of bodyweight gain. Furthermore, the induction of leptin secretion may have an important impact on bodyweight gain in patients treated with atypical antipsychotics. Drug Saf 2001 Jan;24(1):59-73; 

       Another meta-analysis of 10 weeks of treatment found that placebo was associated with a mean weight reduction of 0.74 kg. Among traditional anti-psychotics, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine (Mellaril). Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Am J Psychiatry 1999 Nov;156(11):1686-96. Men with schizophrenia have mean BMIs similar to those of men without schizophrenia (26.14 vs. 25.63, respectively). In contrast, women with schizophrenia in the NHIS data set had a significantly (p<.001) higher mean BMI than did women without schizophrenia (27.36 vs. 24.50, respectively). Moreover, each decile was higher for women with schizophrenia than for women without schizophrenia. Analysis of the ziprasidone and NHANES III data sets revealed that, on average, men with schizophrenia have mean BMIs comparable to those of men without schizophrenia (26.79 vs. 26.52, respectively). In these 2 data sets, women with schizophrenia also had a mean BMI similar to those of women without schizophrenia (27.29 vs. 27.39, respectively). J Clin Psychiatry 1999 Apr;60(4):215-20

Gradual Switch from Clozapine to Ziprasidone or Olanzapine Shown to Work Best: Due to withdrawal symptoms, clozapine is the only atypical agent recommended to proceed with a slow dose taper when switching to another atypical drug. Sudden cessation could also precipitate the emergence of motor symptoms, which can include pseudoparkinsonism, dystonia, akathisia, and dyskinesia. Olanzapine study revealed optimal benefits when the previous agents were gradually withdrawn and olanzapine was initiated at 10 mg/day. The ziprasidone switch study demonstrated both reduced adverse side effects from the previous agents and improvements in clinical efficacy. Additional studies are needed to examine the optimal methods for switching patients from one atypical agent to another atypical antipsychotic. Clinical significance of drug binding, protein binding, and binding displacement drug interactions. Jann MW. Psychopharmacol Bull 2002 Summer;36(3):22-41

Case of Oculogyric Crisis: J Am Acad Child Adolesc Psychiatry. 2003 Sep;42(9):1013-4

Case of Galactorrhea in Teen: J Am Acad Child Adolesc Psychiatry. 2003 Jan;42(1):4-5. This is a common side-effects of Risperdal and traditional anti-psychotics, but rare with Geodon.

Lupus Case Reported from Ziprasidone:  Swensen E, Ravasia S. Can J Psychiatry. 2004 Jun;49(6):413-4.  

Patients Stayed on Geodon Better with Lower Costs: Medical and pharmacy claims data were used to compare persistence (days of therapy between first and last prescriptions); compliance (ratio of days of medication supplied to total days on therapy); and treatment costs in 1,810 adults with schizophrenia. Persistence was 31 days longer for patients receiving ziprasidone (228 days) than risperidone (193 days) or olanzapine (201 days). Compliance was significantly (P<.05) higher among patients receiving ziprasidone (87%) compared with other treatments (78%-80%). Ziprasidone patients had significantly larger decreases (-$6866) in mean annual psychiatric-related costs following therapy initiation than those on risperidone (-$3353; P = .0116) or olanzapine (-$4764; P = .0021). The primary driver of cost savings was reduced hospitalization after treatment initiation. Impact of atypical antipsychotics on outcomes of care in schizophrenia. Joyce AT, et al. PharMetrics, Watertown, Massachusetts 02472. Am J Manag Care. 2005 Sep;11(8 Suppl):S254-61. Am J Manag Care. 2005 Sep;11(8 Suppl):S254-61. 

Cost Lower with Quetiapine or Ziprasidone vs Olanzapine or Risperidone: Quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of $530, and $485 respectively. Side-effects of olanzapine and risperidone blamed. Univ Hull. Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost. Mortimer A, Williams P, Meddis D. J Int Med Res. 2003 May-Jun;31(3):188-96; Ed: Ziprasidone appears least expensive due to cost savings of one-a-day dosing, but good studies of the issue are not available. Above study seems speculative.

Tardive Dyskinesia: Resolution of Ziprasidone-Related Tardive Dyskinesia With a Switch to Aripiprazole: Sharma A, Ramaswamy S, Dewan VK. Creighton-Nebraska. Prim Care Companion J Clin Psychiatry. 2005;7(1):36.

Torsades de Pointes: FDA Has Received a Few Reports of Unexplained Deaths: FDA said it received several spontaneous reports of heart beat abnormalities and reports of unexplained sudden deaths among Geodon users.  I have been unable to find any numbers, but small numbers of unexplained deaths or deaths from known side-effects occur with many other medications including buproprion (Wellbutrin), olanzapine (Zypreza: due to olanzapine induced diabetes), desipramine, haloperidol (Haldol), and probably most other psychiatric medications.  I doubt that the death rate on Geodon is any higher than any other anti-psychotic and I think it is almost certainly much lower than the death rate in similar patients treated without an anti-psychotic. For that matter, aspirin probably causes thousands of deaths each year due to increased rates of hemorragic strokes but its good effects may outweigh its bad effects.

Torsades de Pointes: First Death Reported: Sudden death in a patient with Tourette syndrome during a clinical trial of ziprasidone. Scahill L, et al. Yale University. J Psychopharmacol. 2005 Jun;19(2):205-6.

Torsades de Pointes: QTc Prolongation Possible from Risperdal, Seroquel, Geodon: The author found nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration involving risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. No evidence of torsades de pointes appeared in any of the 9 cases. New Generation Antipsychotic Drugs and QTc Interval Prolongation. Vieweg WV. Medical College of Virginia. Prim Care Companion J Clin Psychiatry. 2003 Oct;5(5):205-215

Torsades de Pointes: High Dose Ziprasidone Not Cause QTc Problem: The maximum dose of 160 mg/day approved by the Food and Drug Administration. In a report of 15 patients given 240 to 320 mg/day, due to intractable psychotic symptoms there was an average increase of 3.4 msec from pre- to post-treatment, with a maximum post-treatment interval of 452 msec and no cases having a pre- to post- treatment QTc interval increase > 20 msec. No significant QTc interval changes with high-dose ziprasidone: a case series. Levy WO, Robichaux-Keene NR, Nunez C. VA Medical Center, Tampa, FL. J Psychiatr Pract. 2004 Jul;10(4):227-32.

Torsades de Pointes Increased with Haldol: Torsade de pointes, a polymorphic ventricular tachyarrhythmia, has been associated with both intravenous and oral haloperidol administration. The management of torsade de pointes consists of discontinuation of haldol, correction of electrolyte abnormalities, administration of magnesium sulfate and, if necessary, overdrive pacing. Torsade de pointes associated with the administration of intravenous haloperidol:a review of the literature and practical guidelines for use. Hassaballa HA, Balk RA. Rush-Presbyterian St Luke's. Expert Opin Drug Saf. 2003 Nov;2(6):543-7. Ed: Haloperidol is associated with a small increase in the rate of sudden death compared to alternative treatments.

Magnesium Supplementation Helps Torsades de Pointes: Saldanha Aoki M, Rodriguez Amaral Almeida AL, Navarro F, Bicudo Pereira Costa-Rosa LF, Pereira Bacurau RF. Ann Nutr Metab. 2004;48(2):90-4. Ed: This suggests that patients on ziprasidone (Geodon) should take magnesium. Of course, I recommend magnesium 250 mg once or twice a day for everyone since the research on the benefits of magnesium supplementation is so positive.

Magnesium: IV Treats Torsade de Pointes; Oral Prophylactically Reduces Extrasystoles: Magnesium is of great importance in cardiac arrhythmias. It increases the ventricular threshold for fibrillation. Sinus node refractoriness and conduction in the AV node are both prolonged. Main indications for intravenous application of magnesium are Torsade de pointes tachycardias, digitalis toxicity induced tachyarrhythmias and multifocal atrial tachycardias. Additionally, patients with ventricular arrhythmias due to overdoses of neuroleptics or tricyclic antidepressants may profit from i.v. magnesium. Monomorphic ventricular tachycardias and ventricular arrhythmias refractory to class III antiarrhythmics have been shown to respond to i.v. magnesium. Recent publications have documented that perioperative use of magnesium can reduce the incidence of arrhythmic events on the atrial and ventricular level. Oral magnesium has been used for many years in patients with symptomatic extrasystoles. Studies show that the incidence of extrasystoles as well as patients' symptoms are reduced during oral magnesium therapy. Significance of magnesium in cardiac arrhythmias. Stuhlinger HG, Kiss K, Smetana R. Universitatsklinik fur Nofallmedizin, Vienna, Austria. Wien Med Wochenschr. 2000;150(15-16):330-4. 

Magnesium: Low Levels Increase Arrhythmias and Torsade de Pointes: Hypomagnesemia is arrhythmogenic when combined with hypokalemia and bradycardia leading to a prolongation of the plateau phase of the action potential; magnesium administration suppresses triggered activities mainly by a direct inhibition of the development of triggered potentials; and lidocaine suppresses triggered potentials only indirectly by preventing the development of early afterdepolarizations due to the shortening effect on the APD. There is a high incidence of torsade de pointes with the hypokalemia and hypomagnesemia caused by a chronic diuretic therapy. There is also the marked effectiveness of intravenous Mg vs. the inconsistent clinical effects of lidocaine in controlling torsade de pointes. Antiarrhythmic and Arrhythmogenic Actions of Varying Levels of Extracellular Magnesium: Possible Cellular Basis for the Differences in the Efficacy of magnesium and Lidocaine in Torsade de Pointes. Takanaka C, Ogunyankin KO, et al. UCLA. J Cardiovasc Pharmacol Ther. 1997 Apr;2(2):125-134.

Magnesium: Low Levels Common Problem: Hypomagnesemia causes neuromuscular, neurological, and psychiatric difficulties as well as cardiac arrhythmias including torsade de pointes resulting in sudden death. Incidence of hypomagnesemia in hospitalized patients is common and there is a lack of clinical awareness. Hypomagnesaemia in postoperative patients: an important contributing factor in postoperative mortality. Siddiqui MN, Zafar H, et al. Aga Khan University, Karachi, Pakistan. Int J Clin Pract. 1998 Jun;52(4):265-7.

Magnesium: Coronary Heart Disease Decreased in Health Professionals by Magnesium: In the Harvard 39,000 male health professional study during 12 years of follow-up, there were 1,021 non-fatal heart attacks, and 428 fatal ones. The age-adjusted relative risk (RR) of developing CHD in the highest quintile (median intake = 457 mg/day) compared with the lowest quintile (intake = 269 mg/day) was 0.73 (p <0.0001). After controlling for standard CHD risk factors and dietary factors, the RR was 0.82 (p = 0.08), i.e., an 18% decrease in heart attacks. For supplemental magnesium intake, the RR comparing the highest quintile to non-supplement users was 0.77, a 23% decrease. Magnesium intake and risk of coronary heart disease among men. Al-Delaimy WK, Rimm EB, Willett WC, Stampfer MJ, Hu FB. J Am Coll Nutr. 2004 Feb;23(1):63-70. Ed: Excellent research shows that higher intakes of magnesium, including with the aid of supplements, results in a lower risk of developing diabetes and hypertension.

Magnesium: Coronary Artery Disease Increased 150% by Low Magnesium Intake: The 7,172 men in the Honolulu Heart Program had a baseline average daily dietary magnesium intake of 268 mg, with a range of 50.3 to 1,138 mg. During 30 years of follow-up, 1431 cases of coronary heart disease were identified. Within 15 years of baseline dietary assessment, the age-adjusted incidence of such disease fell significantly in those with the highest daily magnesium intake (340 mg or more) compared to those with the lowest (186 mg or less) or an incidence of 4.0 per 1000 person-years versus 7.3 per 1000 person-years. After adjustment for a variety of other elements, including nutrient intake and cardiovascular risk factors, the excess risk in those with the lowest intake ranged from 1.5 to 1.8-fold. Robert D. Abbott, University of Virginia. Am J Cardiol 2003;92:665-669

Magnesium Supplementation Helps Heart: Studies indicate an association between magnesium deficiency and a poor prognostic outcome in patients who have had myocardial infarction. It therefore appears to be a reasonable prophylactic measure to monitor closely magnesium status in patients with coronary heart disease and other patients at risk of acute myocardial infarction, and to supplement with oral magnesium when clinically necessary. In addition, recent studies provide supportive evidence that supplementation of magnesium may reduce the incidence of fatal and nonfatal arrhythmias after an infarct. Case Western, Am J Cardiol 1989 Apr 18;63(14):35G

Magnesium: Magnesium Supplement Helps Blocked Coronaries: A Los Angeles study of oral magnesium supplement found that it increased blood flow and lengthened exercise tolerance in DB study of patients with blocked coronaries. Circ 2000;102:2353

Magensium: Coronary Artery Disease Helped by Magnesium in DB: In a DB PC study of 181 patients with half on 365 mg/day of magnesium, researchers found not just improved endothelium with the magnesium but also improved exercise tolerance with a decrease in chest pain and improved quality of life. Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease. Shechter M, Bairey Merz CN, Stuehlinger HG, Slany J, Pachinger O, Rabinowitz B. Am J Cardiol. 2003 Mar 1;91(5):517-21.

Hypokalemia Prolongs QTc: Even modest low potassium levels of 2.8-3.4 mmol/L can prolong the QTc interval and trigger torsade de pointes with other conditions, such as a congenital long QT syndrome or one case of a 54 year old man with schizophrenia on ziprasidone 160 mg/day admitted to the hospital for rhabdomyolysis due to a potassium of just 2.0 and a QTc of 550 msec. 

12,800-mg ziprasidone overdose without significant ECG changes:  Gen Hosp Psychiatry. 2005 May-Jun;27(3):222-3.

Resolution of Ziprasidone-Related Tardive Dyskinesia With a Switch to Aripiprazole: Prim Care Companion J Clin Psychiatry. 2005;7(1):36.

Case: Ziprasidone-induced priapism requiring surgical treatment. Eur Psychiatry 2005 Dec 12.

Cases: Lithium intoxication associated with intramuscular ziprasidone in two schizoaffective patients. Clin Neuropharmacol 2005 Nov-Dec;28(6):295-7.

Ziprasidone Can Cause Manic Swing: This makes 8 reports of ziprasidone-induced mania in 14 patients. Of the 14 cases, 9 were in a depressive episode when ziprasidone was prescribed, and 8 had a history of current or past exposure to antidepressants. Ziprasidone, like many antidepressants, can block reuptake of norepinephrine and serotonin, although mania has developed in patients treated with atypical antipsychotics that are less potent in this regard. Ziprasidone and other atypical antipsychotics have in common a high ratio of 5-HT2a to D2 receptor blockade, which may also play a role. Ziprasidone-associated mania: a review and report of 2 additional cases. Keating AM, et al. University of Minnesota. Clin Neuropharmacol. 2005 Mar-Apr;28(2):83-6.

Ziprasidone Called Safe Up to 320 mg/day: The Physician's Desk Reference (PDR) was established to provide for the practicing of a complete listing of all medications with the FDA-approved labelling, including dosage recommendations. Perhaps in order to maximise individual usage of medications, pharmaceutical companies have frequently targeted lowest possible doses for FDA approval. However, many patients with a variety of illnesses due to resistance and/or multiple illnesses, may need higher than these dose ranges. Only risperidone initially obtained approval for a dose for psychosis (16 mg) higher than that suggested currently (maximum of 8 mg). The dose that was approved for mania was lower: a maximum of 6 mg. The others: respectfully, olanzapine (schizophrenia: 15 mg, mania: 20 mg), quetiapine (schizophrenia: 750 mg; mania: 800 mg), ziprasidone (schizophrenia and mania: 160 mg) and aripiprazole (schizophrenia and mania: 30 mg) obtained approvals for psychosis that may limit adverse events but, at the same time, limit benefits. Other data from various sources (double-blind trials, open-label trials, reviews and case reports) have found safety and/or efficacy for the following maximum doses: olanzapine (40 mg), quetiapine (1600 mg), ziprasidone (320 mg) and aripiprazole (75 mg). In many situations, feared increase in adverse events were not magnified by use of higher doses. Higher than Physician's Desk Reference (US) doses on atypical antipsychotics. Goodnick PJ. UMDNJ Robert Wood Johnson School of Medicine. . Expert Opin Drug Saf 2005 Jul;4(4):653-68.

Geodon^® Patient Assistance Program provides assistance to uninsured patients who are at or below 200% of the federal poverty level and have no access to other forms of public or private reimbursement for pharmaceuticals. The Geodon Patient Assistance Program helps prescribers facilitate treatment for their patients through reimbursement support, alternate funding searches, and with prescription assistance to uninsured patients below 200% of the federal poverty level.  Physicians interested in utilizing the program should call 1-866-443-6366. M-F 9 a.m.-8 p.m. E.S.T.

Thomas E. Radecki, M.D., J.D.

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