1. Copyright Notice
This presentation is copyrighted by the Psychopharmacology Institute.
Subscribers can download it and use it for professional use.
The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

2. Adverse Effects of Antipsychotics in Elderly Patients
Sandra A. Jacobson, M.D.
Research Associate Professor
University of Arizona College of Medicine Phoenix

3. Antipsychotics: “big guns” among psychotropics
Huybrechts KF, Gerhard T, Crystal S, et al.: Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ 344:e977, 2012

4. Antipsychotics: “big guns” among psychotropics
Significant morbidity and mortality
Fully informed consent is essential
Huybrechts KF, Gerhard T, Crystal S, et al.: Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ 344:e977, 2012

5. Antipsychotics: “big guns” among psychotropics
Significant morbidity and mortality
Fully informed consent is essential
Mortality risk
Greatest when:
drug is initiated
dose is increased
Huybrechts KF, Gerhard T, Crystal S, et al.: Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ 344:e977, 2012

6. QTc prolongation, sedation
Orthostatic hypotension
Anticholinergic effects
Metabolic effects
Extrapyramidal effects

7. Dose and level dependent
Increased risk of sudden death
Females: QTc > 470 msec
Males: QTc > 450 msec
QTc prolongation
Washington NB: Which psychotropics carry the greatest risk of QTc prolongation? Curr Psychiatry 11:36-39, 2012

8. Dose and level dependent
Increased risk of sudden death
Females: QTc > 470 msec
Males: QTc > 450 msec
Aripiprazole: the least QTc prolonging
Mesoridazine and thioridazine: the most QTc prolonging
QTc prolongation
Washington NB: Which psychotropics carry the greatest risk of QTc prolongation? Curr Psychiatry 11:36-39, 2012

9. Orthostatic hypotension
Risk of falling, myocardial infarction and stroke
Develops early in treatment
Patients don’t become tolerant
Orthostatic hypotension
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

10. Orthostatic hypotension
Risk of falling, myocardial infarction and stroke
Develops early in treatment
Patients don’t become tolerant
If baseline orthostasis
Drugs with low affinity for the alpha-1 receptor
Aripiprazole, lurasidone or ziprasidone
Orthostatic hypotension
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

11. Orthostatic hypotension
Risk of falling, myocardial infarction and stroke
Develops early in treatment
Patients don’t become tolerant
If baseline orthostasis
Drugs with low affinity for the alpha-1 receptor
Aripiprazole, lurasidone or ziprasidone
Can be minimized:
Small, divided oral doses and slow titration
Orthostatic hypotension
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

12. Anticholinergic effects
Constipation, urinary retention, glaucoma exacerbation, disorientation, memory impairment and increased postural sway
Anticholinergic effects

13. Anticholinergic effects
Constipation, urinary retention, glaucoma exacerbation, disorientation, memory impairment and increased postural sway
Higher risk
Low baseline cholinergic function
Alzheimer’s disease
Lewy body dementia
Carriers of apolipoprotein E4 allele
Anticholinergic effects

14. Weight gain, glucose dysregulation, dyslipidemia
Metabolic effects
Hasnain M, RV WV, Hollett B: Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 124: , 2012

15. Weight gain, glucose dysregulation, dyslipidemia
Some patients meet criteria for metabolic syndrome.
Clozapine and olanzapine
Greatest risk of weight gain and glucose dysregulation
Aripiprazole, asenapine, lurasidone, paliperidone and ziprasidone
Metabolic effects
Lowest risk.
Hasnain M, RV WV, Hollett B: Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 124: , 2012

16. Weight gain, glucose dysregulation, dyslipidemia
Some patients meet criteria for metabolic syndrome.
Clozapine and olanzapine
Greatest risk of weight gain and glucose dysregulation
Aripiprazole, asenapine, lurasidone, paliperidone and ziprasidone
Lowest risk.
Implement: pre-screening, monitoring and intervention protocols for metabolic syndrome
Metabolic effects
Hasnain M, RV WV, Hollett B: Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 124: , 2012

17. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Extrapyramidal effects

18. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Usually after a week of treatment
Extrapyramidal effects

19. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Usually after a week of treatment
Clozapine: devoid of EPS
Extrapyramidal effects

20. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Usually after a week of treatment
Clozapine: devoid of EPS
Iloperidone and quetiapine: low risk
Extrapyramidal effects

21. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Usually after a week of treatment
Clozapine: devoid of EPS
Iloperidone and quetiapine: low risk
Dose-dependent
Extrapyramidal effects
Lower dose or stop

22. Extrapyramidal effects
Prominent bradykinesia, rigidity, impaired righting reflex, dysphagia, autonomic instability, drooling and seborrhea
Usually after a week of treatment
Clozapine: devoid of EPS
Iloperidone and quetiapine: low risk
Dose-dependent
Lower dose or stop
Routine prophylaxis with anticholinergic drugs: not recommended
Extrapyramidal effects
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

23. Clozapine

24. Agranulocytosis also can be seen
Hypotension
Sedation
Aspiration
Agranulocytosis also can be seen
Clozapine
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

25. Antipsychotics in geriatrics
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

26. Antipsychotics in geriatrics
Condition being treated
Comorbidities (e.g. diabetes or obesity)
Prior response to treatment
Non-adherence: might be an indication for a long-acting injectable drug
Antipsychotics in geriatrics
Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.

27. Key Points Orthostatic hypotension
Aripiprazole, lurasidone and ziprasidone have low affinity for alpha-1 receptors

28. Key Points Orthostatic hypotension
Aripiprazole, lurasidone and ziprasidone have low affinity for alpha-1 receptors
Can be minimized using small, divided oral doses and titrating slowly

29. Key Points Orthostatic hypotension Metabolic effects
Aripiprazole, lurasidone and ziprasidone have low affinity for alpha-1 receptors
Can be minimized using small, divided oral doses and titrating slowly
Metabolic effects
Aripiprazole, asenapine, lurasidone, paliperidone and ziprasidone confer the least risk

30. Key Points Orthostatic hypotension Metabolic effects
Aripiprazole, lurasidone and ziprasidone have low affinity for alpha-1 receptors
Can be minimized using small, divided oral doses and titrating slowly
Metabolic effects
Aripiprazole, asenapine, lurasidone, paliperidone and ziprasidone confer the least risk
Extrapyramidal effects
Quetiapine and iloperidone confer a low risk
Clozapine is devoid of EPS

31. Next Presentation - Antidepressants: Focus on Geriatric Depression, Drug Selection, Formulations and Treatment Resistance