Ziprasidone in the treatment of mania in bipolar disorder

Figures & data

Table 1 Safety and Tolerability Trial I (Keck et al 2003)

	Placebo Group	Ziprasidone Group
Number of patients	66	131
Mean Age (range)	37 (19–64)	39 (18–66)
Bipolar Episode Manic/Mixed	63%/37%	65%/35%
Baseline MRS	26.7	27.0
Mean reduction MRS	7.8	12.4 (p < 0.005)
Responders	35%	50% (p < 0.05)
Reduction in CGI severity	0.9	1.3 (p < 0.01)
Reduction in PANSS	2.0	4.8 (p < 0.001)
Discontinuation Rates	55.7%	46.4% *
Withdrawal secondary to adverse events	4.3%	6.4% *
Adverse Events, total	77.1%	90.0% *
Somnolence	12.9%	37.1% *
Headache	18.6%	21.4% *
Dizziness	10.0%	22.1% *
Hypertonia	2.9%	11.4% *
Nausea	10.0%	11.4% *
Akathisia	5.7%	10.7% *
Mean QTc	Not reported	11 msec

* p value not provided.

Average ziprasidone dose during days 15–21: 130.1mg/day.

Table 2 Safety and Tolerability Trial II (Potkin et al 2005)

	Placebo Group	Ziprasidone Group
Number of patients	66	139
Mean Age (range)	39 (10–71)	39 (19–70)
Bipolar Episode Manic/Mixed	61%/39%	59%/41%
Baseline MRS	26.4	26.2
Reduction in MRS	5.6	11.1 (p < 0.01)
Reduction in CGI severity	0.43	1.09 (p ≤ 0.001)
Reduction in PANSS	3.55	12.01 (p ≤ 0.01)
Discontinuation Rates	46%	39% *
Treatment-related discontinuation	1.5%	5.8% (p = 0.20)
Adverse Events, total	67%	78% *
Somnolence	6.1%	22.3% (p = 0.002)
Headache	7.6%	12.2% (p = 0.122)
Extrapyramidal Syndrome	1.5%	10.8% (p = 0.013)
Dizziness	1.5%	10.1% (p = 0.018)
Akathisia	4.5%	9.4% (p = 0.167)
Nausea	1.5%	6.5% (p = 0.094)
Asthenia	1.5%	5.0% TK
Abdominal Pain	7.6%	1.4% TK
Mean Lengthening of QTc	2.1msec	10.1 msec
Median Weight Change	0 kg	0 kg
Weight Gain ≥7%	3.4%	4.8% *
Mean change in total cholesterol	−1mg/dL	1mg/dL
Mean change in total triglycerides	−8 mg/dL	−1mg/dL

* p value not provided.

Average ziprasidone dose during days 15–21: 126.5 mg/day.

Overall mean ziprasidone dose: 112 mg/day.

Figure 1 Mean decrease in MRS pure mania vs mixed episodes after 21 days (estimated from Potkin et al 2004).

Figure 2 Decrease in MRS psychotic mania vs non-psychotic mania after 21 days (estimated from Potkin et al 2004).

Table 3 Ziprasidone augmentation with lithium (Weisler et al 2003)

	Lithium + Placebo Group	Lithium + Ziprasidone Group
Number of Patients	103	102
Mean Age in yrs (range)	37 (18–70)	37 (19–71)
Type of Manic Episode: Pure/Mixed	68%/32%	61%/39%
Discontinued	28.2%	30.7% *
Mean reduction MRS (at 4 days)	1.59	2.31 (p < 0.05)
Mean reduction MRS (at 14 days)	5.51	6.5 (not statistically significant)
Reduction in CGI severity (at 4 days)	0.12	2.0 (p < 0.01)
Reduction in PANSS (at 21 days)	8.45	13.4 (p < 0.01)
Withdrawal secondary to adverse events	4%	8% *
Adverse Events, total	76%	86% *
Somnolence	12%	34% *
Extrapyramidal Syndrome	4%	22% *
Dizziness	6%	13% *
Agitation	2%	11% *
AbnormalVision	4%	10% *
Vomitting	5%	10% *
Akathisia	0%	9% *
Dystonia	0%	9% *
Mean Lengthening of QTc	6.1 msec	11.8 msec

* p value not provided.

Average ziprasidone dose: 131.1 mg/day.

Table 4 Adjunctive ziprasidone with lithium 52-week open label extension (Weisler et al 2004)

Number of patients at extension study baseline	89 (41 from ziprasidone + lithium, 48 from placebo + lithium)
Mean age in years (range)	37 (18–71)
Episode at Acute Study baseline Pure Mania/Mixed	46%/54%
Reduction in MRS at 52 weeks for those from ziprasidone arm of acute study (n = 10)	20.70 (p < 0.01)
Gained ≥7% of baseline body weight	12.1 %
Lost ≥7% of baseline body weight	10.6%
Mean change in weight	−0.76 lbs *
Mean change in serum triglycerides	−43.27 (p = 0.01)
Discontinuation rate	56%
Discontinuation rate due to adverse events	12.4%
Adverse Events	90.0%
Somnolence	55.1%
AbnormalVision	23.6%
Tremor	22.5%
EPS	21.3%
Dizziness	20.2%

* p value not provided.

Mean ziprasidone dose at 52 weeks (n = 10): 92.6 mg/day.

Table 5 Ziprasidone 52-week open label extension (Keck et al 2004)

Number of Patients	127
Mean Age in yrs (range)	39 (18–66)
Type of Manic Episode: Pure/Mixed	69%/31%
Discontinued	62.2%
Withdrawal secondary to adverse events	8.7%
Mean Change in plasma cholesterol	1.59 mg/dl
Mean Change in plasma triglycerides	−14.8 mg/dl
Mean Weight Change	−2.52 kg
Weight Gain ≥ 7%	11.0%
Weight Gain ≤ 7%	11.0%

Mean ziprasidone dose: 122.4 mg/day.

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