atypical or second generation neuroleptics n.
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Atypical or Second Generation Neuroleptics. Period 4: BPRS Total Score During Double-Blind Period. Which Term Should We Use?. Atypical (implies an unusual mechanism of action—e.g., minimal dopamine blockade or combined dopamine serotonin blockade) Novel (implies new, tho Clozapine is “old”)

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which term should we use
Which Term Should We Use?
  • Atypical (implies an unusual mechanism of action—e.g., minimal dopamine blockade or combined dopamine serotonin blockade)
  • Novel (implies new, tho Clozapine is “old”)
  • Second generation (perhaps the most neutral term…but too many syllables)
combined dopamine and serotonin antagonists
Combined Dopamine and Serotonin Antagonists
  • Clozapine (weak D2)
  • Risperidone
  • Olanzapine
  • Quetiapine (weak D2)
  • Ziprasidone
  • Sertindole
  • Zodepin
the atypical era total antipsychotic prescriptions in us
The Atypical Era:Total Antipsychotic Prescriptions in US

Older generation

Totalprescriptions(000’s)

Atypical

*

*projected linear trending from 1996, 1997, 1998

Levin 1999

european psychiatrists preferred treatment for a member of their family
European Psychiatrists’ Preferred Treatment for a Member of Their Family

0 20 40 60 80 100

Smith-Laittan and Grundy, 1999

advantages of atypical neuroleptics
Advantages of Atypical Neuroleptics
  • Broader therapeutic spectrum
    • therapeutic efficacy on
      • positive symptoms
      • refractory — residual
    • reduction, prevention:
      • negative (deficit) syndrome
      • depressive symptoms
      • cognitive deficits
  • No (fewer) side effects
    • objective: acute EPS, TD
    • subjective: dysphoric response
more advantages of atypical neuroleptics
More Advantages of Atypical Neuroleptics
  • Earlier treatment for first episode (prevention?)
  • More acceptable to take, less stigma
  • Earlier and better participation in psychosocial rehabilitation programs
  • Higher compliance, less relapse/rehospitalization
  • Higher level of reintegration, better quality of life
reasons to switch from classical to second generation neuroleptics
Reasons to Switch From Classical to Second Generation Neuroleptics
  • Inadequate response of positive symptoms
  • Residual negative symptoms
  • Associated mood symptoms (e.g. depression)
  • Residual or unresponsive cognitive symptoms
  • Relapse, despite compliance
  • Non-compliance due to adverse events
  • Patient/family request
switching from classical to second generation neuroleptics
Switching From Classical to Second Generation Neuroleptics

Reduction in use of anticholinergic drugs for EPS

100

75

50

25

0

*p<0.01

Patients using anticholinergicdrugs for EPS (%) (n=31)

*

Switch

Conventional

neuroleptics

(t=41.1 months)

Risperidone

(t=20.1 months)

Malla A et al. Clin Ther 1999;21(5):806–17

incidence of td in elderly subjects treated with conventional neuroleptics or risperidone
Incidence of TD in Elderly Subjects Treated With Conventional Neuroleptics or Risperidone

*Includes elderly patients with dementia

weight changes with atypical neuroleptics
Weight Changes With Atypical Neuroleptics

5

t=10 weeks

4

3

Mean change in body weight (kg)

2

1

Control Risperidone Olanzapine Clozapine

*For marketed drugs

After Allison DB et al. Am J Psychiatry 1999;156(11):1686–96

possible consequences of weight gain in schizophrenia
Possible Consequences of Weight Gain in Schizophrenia
  • Cardiovascular morbidity and mortality
  • Psychosocial distress
  • Non-compliance with treatment
  • Further increased risk of diabetes