Safety and Tolerability

1
Safety and Tolerability
2
Safety and TolerabilityConcerns With
Antipsychotics

• EPS
• Hyperprolactinemia
• Somnolence/sedation
• Weight gain
• Diabetes
• Dyslipidemias

Keck PE Jr, et al. J Clin Psychiatry.
200061(suppl 4)33-38.
3
Potential Consequences of EPS

• Motor and cognitive impairment1
• Need for anticholinergic medications1
• Increased risk of tardive dyskinesia (TD)2
• Increased secondary negative symptoms2
• Nonadherence and relapse2,3

1. Goff DC et al. Med Clin North Am.
200185663-689. 2. Kapur S et al. Annu Rev Med.
200152503-517. 3. Worrel JA et al. Am J Health
Syst Pharm. 200057238-255.
4
How Important Are EPS Side Effects?
Differences in VAS Comparing EPS and No EPS
Videotaped Patient Scenarios
0.16
Patients
0.14
More
Families
0.12
Clinicians
0.1
0.08
0.06
Degree of Impact From EPS Shown on Video
0.04
0.02
0
More Severe States
Milder States
VAS Visual Analog Scale where a score of 1
perfectly healthy and 0 death
Lenert LA et al. Med Care. 2000381011-1021.
5
Potential Clinical Sequelae of Hyperprolactinemia
Maguire GA. J Clin Psychiatry. 200263(suppl
4)56-62.
6
Somnolence Good or Bad?

• Somnolence may correlate with affinity for
  H-receptors
• Inducing somnolence may be a desirable short-term
  effect for acutely manic or highly irritable
  patient
• Sedating clozapine, olanzapine, quetiapine
• Less sedating risperidone
• Activating ziprasidone, aripiprazole

Moller HJ, Nasrallah HA. J Clin Psychiatry.
200364(suppl 6)9-17.
7
Significant Weight GainShort- and Long-Term
Implications

• Increased risk of
• Coronary heart disease
• Hypertension
• Type 2 diabetes
• Dyslipidemias
• Stigma associated with obesity
• Nonadherence with treatment

Kurzthaler I, Fleischhacker WW. J Clin
Psychiatry. 200162(suppl 7)32-37.
8
Meta-analysis of Antipsychotics-Related Weight
Gain Estimate at 10 Weeks
Weight (kg)
7 6 5 4 3 2 1 0 -1 -2 -3
95 Confidence Interval for Weight Change
Placebo
Clozapine
Thioridazine/ Mesoridazine
Molindone
Olanzapine
Ziprasidone
Haloperidol
Risperidone
Quetiapine
Fluphenazine
Chlorpromazine
Quetiapine weight gain estimated at 6 weeks
Adapted from Allison DB et al. Am J Psychiatry.
19991561686-1696.
9
The Effects of Atypical Antipsychotics on
Glucose and Lipid Levels
Retrospective Study 215 Patients With
Glucose/Lipid Levels 2.5 Years Before Treatment
and After Treatment
50
40
30
Percentage of Patients
20
10
0
Clinically Significant Decreases in HDL
Random Blood Glucose gt 200 mg/dL
Clinically Significant Elevations in Total
Cholesterol
Wirshing DA et al. J Clin Psychiatry.
200263856865.