1- Who are Geriatrics? 2- Why are they considered a specific group? 3- Pharmacokinetic and Pharmacodynamic changes in Geriatrics 4- Changes of the aged brain. 5- Psychiatric drugs using in Geriatrics in: - Depression and Anxiety - Mania - Schizophrenia and Psychosis - Mild cognitive impairment and Dementia

4. Contents
• 1- Who are Geriatrics?
• 2- Why are they considered a specific group?
• 3- Pharmacokinetic and Pharmacodynamic
changes in Geriatrics
• 4- Changes of the aged brain.
• 5- Psychiatric drugs using in Geriatrics in:
- Depression and Anxiety
- Mania
- Schizophrenia and Psychosis
- Mild cognitive impairment and Dementia

5. Who are Geriatrics?
• Dictionaries define 'geriatric' as 'pertaining to
old people' and the World Health Organization
(1963) has defined 'middle-age' as being 45-
59 years, 'elderly' as being 60-74 years and the
'aged' as over 75 years of age.
• Persons aged 60y and older constitute 15% of
the population and purchase 33% of all
prescription medications

6. In the United States, primary care providers that
are board certified in either family practice or
internal medicine and also have completed
the training required to receive a Certificate of
Added Qualifications in geriatric medicine are
known as geriatricians

7. What do specify Geriatrics?
• They have some specific issues:
* A specific kind of Pharmacokinetics
* A specific kind of Pharmacodynamics
* A specific kind of Adverse effects
*Polypharmacy and drug-drug interaction.
*General medical conditions (co-morbidities)
*Compliance on treatment.
*Cost of drugs.

8. PHARMACOKINTICS IN GERIATRICS
This means how drug is affected
by the body

9. • Absorption
– bioavailability: the fraction of a drug dose reaching the
systemic circulation
• Distribution
– locations in the body a drug penetrates expressed as
volume per weight (e.g. L/kg)
• Metabolism
– drug conversion to alternate compounds which may be
pharmacologically active or inactive
• Elimination
– a drug’s final route(s) of exit from the body expressed in
terms of half-life or clearance

10. 1- Absorption
• Changes
↓ swallowing;
↓ gastric emptying;
↓ intestinal motility
↓ absorptive surface;
↓ mesenteric blood flow
↑ gastric pH;
↑ transit time;

11. • Effects
↓ Rate of absorption
Bioavailability may be altered
*Worsened by anticholinergic drugs, antacids, or
co-administration with food
• Implications
Onset of actions is delayed
Clinical effect is reduced if absorption is incomplete
Factors that reduce absorption should be minimized

12. Factors affecting Absorption
• Route of administration
• What it taken with the drug
– Divalent cations (Ca, Mg, Fe)
– Food
– Drugs that influence gastric pH
– Drugs that promote or delay GI motility
• Comorbid conditions
• Increased GI pH
• Decreased gastric emptying
• Dysphagia

13. 2-Distribution
• Changes
↓ muscle mass;
↓ total body water
↑ total body fat

14. Effects
• ↑ Total body fat leads to increased Vd of most
lipophilic drugs, resulting in ↑ t1/2
• Effect of decreased total body H2O increasing
half-life of some drugs such as Li+
Implications
• Longer treatment interval is needed to reach
therapeutic level
• Single doses of agents have a decreased duration
of action due to redistribution into fat stores.

15. Protein binding
• Changes
↓ albumin;
↑ α-1 glycoprotein
• Effects
- Effects of [free drug] vary on whether drug is protein-bound,
binds preferentially to albumin or α-1 glycoprotein, or whether
hepatic clearance is restricted to unbound drug or not.
- Competition for protein-binding sites by drugs may cause
increases in free drug in Plasma
• Implications
- Potentially more potency/toxicity for neuroleptics
- Greater effects may occur in malnourished pts or those with co-
morbid medical conditions
- Increase surveillance for adverse effects when adding new
medications

16. 3- Metabolism
• Changes
↓ Liver volume;
↓ Hepatic blood flow
↓ Oxidative metabolism
↓ N-demethylation

17. Effects
• ↓ metabolism results in ↑peak and plasma levels
• Increased ratio of parent drug to demethylated
metabolite(s).
Implications
• Reductions in CYP450 enzymes may result from genetic
polymorphisms, age-related diseases, or inhibition
from other medications
• Reduced dosages of drugs may be needed (especially
upon initiation). Proceed with caution when increasing
dose and adding additional medications.

18. Other Factors Affecting Drug
Metabolism
• Gender
• Comorbid conditions
• Smoking
• Diet
• Race

19. 4- Elimination
Concepts in Drug Elimination
• Half-life
– time for serum concentration of drug to decline by
50% (expressed in hours)
• Clearance
– volume of serum from which the drug is removed
per unit of time (mL/min or L/hr)
• Reduced elimination  drug accumulation
and toxicity

20. Aging and the Kidney
• Changes
↓ Renal blood flow;
↓ GFR

21. Effects
• Decreased renal clearance leads to longer t1/2
and greater steady state plasma levels
• Drug interactions from diuretics and NSAIDs may
further increase half-life and steady state levels.
(e.g. with Li+)
Implications
• Evaluate renal function before initiation of drugs
dependent upon renal excretion (e.g. Li+)
• Common illnesses may worsen renal Cl
• Reduce doses when necessary
• Toxicity should be monitored in pts with renal
failure

22. Estimating GFR in the Elderly
• Creatinine clearance (CrCl) is used to estimate
glomerular filtration rate
• Serum creatinine alone not accurate in the elderly
–  body mass  lower creatinine production
–  glomerular filtration rate
• Serum creatinine stays in normal range, masking
change in creatinine clearance

23. PHARMACODYNAMICS IN GERIATRICS
This means how drug affects the body

24. • Age-related changes:
–  sensitivity to sedation and psychomotor
impairment with benzodiazepines
–  level and duration of pain relief with narcotic
agents
–  HR as in response to beta-blockers
–  sensitivity to anti-cholinergic agents
–  cardiac sensitivity

25. CNS
• Sedation, confusion, disorientation, memory impairment,
delirium
CVS
• Hypotension, orthostasis, cardiac conduction abnormalities
(arrhythmias, QTc prolongation)
Peripheral anticholinergic effects
• Constipation, dry mouth, blurred vision, urinary retention
Motor effects
• EPS, tremor, impaired gait, increased body sway, falling
Other
• Agitation, mood and perceptual disturbances, headache,
sexual dysfunction, GI (N/V, anorexia, appetite changes,
bowel changes), metabolic, endocrine, electrolyte changes

26. PK and PD Summary
• PK and PD changes generally result in
decreased clearance and increased sensitivity
to medications in older adults
• Use of lower doses, longer intervals, slower
titration are helpful in decreasing the risk of
drug intolerance and toxicity
• Careful monitoring is necessary to ensure
successful outcomes

27. Optimal Pharmacotherapy
• Balance between overprescribing and
underprescribing
– Correct drug and avoid starting with 2 agents in
the same time
– Correct dose
– Targets appropriate condition
– What Is appropriate for the patient
Avoid “a pill for every ill”
Always consider non-pharmacologic therapy

28. Changes of aged brain
• There is neuronal loss in the brain throughout life (the
amount & location varies).
– Loss is chiefly gray matter rather than white matter
– there is some evidence that although some neuronal loss occurs
with age, many neurons have ↑ dendrite growth which may (at
least partially) compensate for neuronal loss in some areas of the
brain.
• Slowed neuronal transmission
• Changes in sleep cycle: takes longer to fall asleep, total time
spent sleeping is less than their younger years, awakenings
throughout the night, increase in frequency of daytime naps

29. Changes in BBB:
• Amino acid transport consists of at least two
components, a fast rate or early process to
transport across the capillary endothelium
and entry into the astrocytes, and a slow rate
or later component measured over 2 to 15
minutes probably associated with exit from
the astrocytes and entry into the neuron.
• The fast rate transport component is
unaffected by age while the rates of the slow
process and protein turnover show an
exponential decline

30. Neuro-chemical changes:
1- Decrease Dopamine and Serotonin synthesis and
re-uptake.
2- Declines in the number of N-methyl-D-aspartate
(NMDA) receptors and alpha-amino-3-hydroxy-5-
methyl-4-isoxazole (AMPA) receptors
3- Decline of GABA, aspartate, glutamine, and
arginine levels which affect sleep and vision
4- Progressive failure of the pineal gland’s capacity
to secrete night time plasma melatonin. The
decline in melatonin secretion with age occurs at
an average rate of 10-15% per decade

31. 5- The levels of neurotransmitters such as
Acetylcholine (ACh) all decreased with age but
this decrease and related metabolic enzyme
activities such as choline acetyltransferase and
choline esterase activities in the brain increase
with age
6- Significant loss of pre-synaptic GABA release
which leads to significant agitation and
irritability.

34. ANTIDEPRESSANTS

35. Treatment selection based on:
• The severity and duration of depression;
• The older adult’s clinical presentation;
• The older adult’s prior history of response to
treatments;
• The presence of other health conditions or
medications;
• The tolerability of the treatments with respect to side
effects or required effort; and
• The older adult’s treatment preferences (including
cost).

36. • No single drug class or ATD has been shown to be more effective in
treating geriatric depression than another.
• Initial doses should be low but “average” adult doses may be
required to achieve adequate response.
• SSRIs are generally considered first-line.
**Most commonly reported adverse events in the elderly are:
insomnia, anxiety, nausea, diarrhea, sexual dysfunction, and
headaches.
**SSRIs may increase the risk of GI bleeding (risk is greatest
within the 1st month of treatment and in patients w/ cirrhosis
or liver failure)
**SSRIs have been linked to SIADH in elderly (monitor Na+)

37. • Venlafaxine, duloxetine and mirtazapine—good alternatives.
**Use caution with venlafaxine in renal failure
**Use caution with duloxetine in hepatic failure
• Bupropion is recommended as a second-line agent.
• TCAs, trazodone and nefazodone are generally not
recommended.
• Efficacy may be delayed in the elderly. Medication trials
generally need to be longer.
• Agents with known drug interactions are less desirable

38. SSRIs

39. Selective Serotonin Reuptake Inhibitors
(SSRIs)
• Block the presynaptic serotonin reuptake
• Treat both anxiety and depressive sx
• Most common side effects include GI upset, sexual
dysfunction (30%+!), anxiety, restlessness,
nervousness, insomnia, fatigue or sedation, dizziness
• Very little risk of cardiotoxicity in overdose
• Can develop a discontinuation syndrome with
agitation, nausea, disequilibrium and dysphoria

40. Fluoxetine
• Pros
– Long half-life so decreased incidence of discontinuation
syndromes. Good for pts with medication noncompliance issues
– Initially activating so may provide increased energy
– Secondary to long half life, can give one 20mg tab to taper
someone off SSRI when trying to prevent SSRI Discontinuation
Syndrome
• Cons
– Long half life and active metabolite may build up (e.g. not a
good choice in patients with hepatic illness)
– Significant P450 interactions so this may not be a good choice in
pts already on a number of meds
– Initial activation may increase anxiety and insomnia
– More likely to induce mania than some of the other SSRIs

41. Escitalopram
• Pros
– Low overall inhibition of P450s enzymes so fewer
drug-drug interactions
– Intermediate 1/2 life
– More effective than Citalopram in acute response and
remission
• Cons
– Dose-dependent QT interval prolongation with doses
of 10-30mg daily
– Nausea, headache

42. Sertraline
• Pros
– Very weak P450 interactions (only slight CYP2D6)
– Short half life with lower build-up of metabolites
– Less sedating when compared to paroxetine
• Cons
– Max absorption requires a full stomach
– Increased number of GI adverse drug reactions

43. Citalopram
• Pros
– Low inhibition of P450 enzymes so fewer drug-drug
interactions
– Intermediate ½ life
• Cons
– Dose-dependent QT interval prolongation with doses of
10-30mg daily- due to this risk doses of >40mg/day not
recommended!
– Can be sedating (has mild antagonism at H1 histamine
receptor)
– GI side effects (less than sertraline)

44. Paroxetine
• Pros
– Short half life with no active metabolite means no build-up
(which is good if hypomania develops)
– Sedating properties (dose at night) offers good initial relief
from anxiety and insomnia
• Cons
– Significant CYP2D6 inhibition
– Sedating, wt gain, more anticholinergic effects
– Likely to cause a discontinuation syndrome

45. Fluvoxamine
• Pros
– Shortest ½ life
– Found to possess some analgesic properties
• Cons
– Shortest ½ life
– GI distress, headaches, sedation, weakness
– Strong inhibitor of CYP1A2 and CYP2C19

46. Serotonin/Norepinephrine reuptake
inhibitors (SNRIs)
• Inhibit both serotonin
and noradrenergic
reuptake like the TCAS
but without the
antihistamine,
antiadrenergic or
anticholinergic side
effects
• Used for depression,
anxiety and possibly
neuropathic pain

47. Venlafaxine
• Pros
– Minimal drug interactions and almost no P450 activity
– Short half life and fast renal clearance avoids build-up (good for
geriatric populations)
• Cons
– Can cause a 10-15 mmHG dose dependent increase in diastolic BP.
– May cause significant nausea, primarily with immediate-release (IR)
tabs
– Can cause a bad discontinuation syndrome, and taper recommended
after 2 weeks of administration
– Noted to cause QT prolongation
– Sexual side effects in >30%

48. Duloxetine
• Pros
– Some data to suggest efficacy for the physical
symptoms of depression
– Thus far less BP increase as compared to
venlafaxine, however this may change in time
• Cons
– CYP2D6 and CYP1A2 inhibitor
– Cannot break capsule, as active ingredient not
stable within the stomach

49. Others

50. Mirtazapine
• Pros
– Different mechanism of action may provide a good augmentation
strategy to SSRIs. Is a 5HT2 and 5HT3 receptor antagonist
– Can be utilized as a hypnotic at lower doses secondary to
antihistaminic effects
• Cons
– Increases serum cholesterol by 20% in 15% of patients and
triglycerides in 6% of patients
– Very sedating at lower doses. At doses 30mg and above it can become
activating and require change of administration time to the morning.
– Associated with weight gain (particularly at doses below 45mg

51. Buproprion
• Pros
– Good for use as an augmenting agent
– Mechanism of action likely reuptake inhibition of dopamine and
norepinephrine
– No weight gain, sexual side effects, sedation or cardiac
interactions
– Low induction of mania
• Cons
– May increase seizure risk at high doses (450mg+) and should
avoid in patients with Traumatic Brain Injury, bulimia and
anorexia.
– Does not treat anxiety unlike many other antidepressants and
can actually cause anxiety, agitation and insomnia
– Has abuse potential because can induce psychotic sx at high
doses

52. Agomelatin
• Pros:
- May not have the same rate or degree or type of side
effects as traditional antidepressants. It may not cause
nausea, sexual dysfunction and other common side effects.
- It may start working faster, with some efficacy observed at
just two weeks, not the four typically needed for
antidepressants.
- Improve sleep quality and has a role in anhedonic
symptoms
• Cons:
- Overall has no significant benefit over Placebo in
treatment of moderate to severe depression.
- Least drug that shown relapse of agitation.

53. TCAs
• Very effective but potentially
unacceptable side effect
profile i.e. antihistaminic,
anticholinergic,
antiadrenergic
• Lethal in overdose (even a one
week supply can be lethal!)
• Can cause QT lengthening
even at a therapeutic serum
level

54. Tertiary TCAs
• Have tertiary amine side chains
• Side chains are prone to cross react with other types of
receptors which leads to more side effects including
antihistaminic (sedation and weight gain), anticholinergic (dry
mouth, dry eyes, constipation, memory deficits and
potentially delirium), antiadrenergic (orthostatic hypotension,
sedation, sexual dysfunction)
• Act predominantly on serotonin receptors
• Examples: Imipramine, amitriptyline, doxepin, clomipramine
• Have active metabolites including desipramine and
nortriptyline

55. Secondary TCAs
• Are often metabolites of tertiary amines
• Primarily block norepinephrine
• Side effects are the same as tertiary TCAs but
generally are less severe
• Examples: Desipramine, nortriptyline

56. • Venlafaxine, duloxetine and mirtazapine—good alternatives.
• Use caution with venlafaxine in renal failure
• Use caution with duloxetine in hepatic failure
• Bupropion is recommended as a second-line agent.
• TCAs, trazodone and nefazodone are generally not recommended.
• Lower anticholinergic effects with secondary amines (e.g. nortriptyline, desipramine)
compared to tertiary amines
• Efficacy may be delayed in the elderly. Medication trials generally need
to be longer.
• Agents with known drug interactions are less desirable
Drug Average Dose Range in Elderly
SSRIs
Citalopram 10-20mg
Escitalopram 10-20mg
Fluoxetine 10-30mg
Fluvoxamine 50-150mg
Paroxetine 10-30mg
Sertraline 25-100mg
SNRIs
Desvenlafaxine 50mg
Duloxetine 10-30mg
Venlafaxine 37.5-150mg
Others
Bupropion 100-250mg
Mirtazapine 7.5-10mg
Vilazodone 10-20mg

58. ANXIOLYTICS

59. • SSRIs are considered to be the drugs of choice
**Drugs with fewer DDIs and favorable PK profiles
are preferred (e.g. citalopram, escitalopram,
sertraline)
**May take 4 to 6 weeks before effective
• Efficacy with venlafaxine XR has been shown,
however caution should be used when treating
patients with renal insufficiency and hypertension
• TCAs—generally avoided

60. • Benzodiazepines
• Frequently used (despite significant adverse effects) due to fast
onset
• If used, lorazepam and oxazepam are preferred because of
short half-lives, no active metabolites, and lack of oxidative
metabolism.
• Problems:
**Cognitive impairment
**Negative effect on gait
**Rebound agitation
• Elderly patients are more vulnerable to the cognitive and
psychomotor effects of benzodiazepines and eliminate long-
acting drugs more slowly than younger patients, and are
predisposed to an increased risk of falls.

61. Drug
Dose Equivalency
(mg)
Peak Blood
Level (hours)
Elimination Half-
Life1 (hours) Comments
Alprazolam (Xanax)
0.5
1-2 12-15 Rapid oral absorption
Chlordiazepoxide
(Librium)
10.0
2-4 15-40
Active metabolites; erratic
bioavailability from IM
injection
Clonazepam
(Klonopin)
0.25
1-4 18-50 Can have layering effect
Diazepam (Valium)
5.0
1-2 20-80
Active metabolites; erratic
bioavailability from IM
injection
Flurazepam (Dalmane)
30.0
1-2 40-100
Active metabolites with long
half-lives
Lorazepam (Ativan)
1.0
1-6 10-20 No active metabolites
Oxazepam (Serax)
15.0
2-4 10-20 No active metabolites
Temazepam (Restoril)
30.0
2-3 10-40 Slow oral absorption
Triazolam (Halcion)
0.25
1
2-3
Rapid onset; short duration of
action

62. Buspirone
• Pros:
– Good augmentation strategy- Mechanism of action is
5HT1A agonist. It works independent of endogenous
release of serotonin.
– No sedation
• Cons:
– Takes around 2 weeks before patients notice results.
– Will not reduce anxiety in patients that are used to take
BZDs because there is no sedation effect to “take the edge
off.

63. MOOD STABILIZERS

64. Lithium
• Only medication to reduce suicide rate.
– Rate of completed suicide in BP Depression ~15%
• Effective in long-term prophylaxis of both mania and
depressive episodes in 70+% of B.P. pts
• Factors predicting positive response to lithium
– Prior long-term response or family member with good
response
– Classic pure mania
– Mania is followed by depression

65. Lithium- how to use it
• Before starting :Get baseline creatinine, TSH and
CBC.
• Monitoring: Steady state achieved after 5 days-
check 12 hours after last dose. Once stable check 3
months …..TSH and creatinine 6 months.
• Goal: blood level between 0.6-1.2

66. Lithium side effects
• Most common are GI distress including reduced appetite,
nausea/vomiting, diarrhea
• Thyroid abnormalities
• Leukocytosis
• Polyuria/polydypsia secondary to ADH antagonism. In a
small number of patients can cause interstitial renal
fibrosis.
• Hair loss, acne
• Reduces seizure threshold, cognitive slowing, intention
tremor
• Drug-Drug interaction with ACEIs and Loop diuretics
which lead to Lithium toxicity

67. Lithium toxicity
• Mild- levels 1.5-2.0 see vomiting, diarrhea,
ataxia, dizziness, slurred speech, nystagmus.
• Moderate -2.0-2.5 nausea, vomiting, anorexia,
blurred vision, clonic limb movements,
convulsions, delirium, syncope
• Severe - >2.5 generalized convulsions, oliguria
and renal failure

68. Anticonvulsants

69. Valproic acid
• Valproic acid is as effective as Lithium in mania
prophylaxis but is not as effective in
depression prophylaxis.
• Factors predicting a positive response:
– rapid cycling patients (females>males)
– comorbid substance issues
– mixed patients
– Patients with comorbid anxiety disorders
• Better tolerated than Lithium

70. Valproic acid
• Before med is started: baseline liver function
tests (lfts),and CBC
• Monitoring: Steady state achieved after 4-5
days -check 12 hours after last dose and
repeat CBC and lfts
• Goal: target level is between 50-125

71. Valproic acid side effects
• Thrombocytopenia and platelet dysfunction
• Nausea, vomiting, weight gain
• Sedation, tremor
• Hair loss

72. Carbamazepine
• First line agent for acute mania and mania
prophylaxis
• Indicated for rapid cyclers and mixed patients

73. • Before med is started: baseline liver function
tests, CBC and an ECG
• Monitoring: Steady state achieved after 5 days
-check 12 hours after last dose and repeat CBC
and lfts
• Goal: Target levels 4-12mcg/ml
• Need to check level and adjust dosing after
around a month because induces own
metabolism.

74. Carbamazepine side effects
• Rash- most common SE seen
• Nausea, vomiting, diarrhea
• Sedation, dizziness, ataxia, confusion
• AV conduction delays
• Aplastic anemia and agranulocytosis (<0.002%)
• Water retention due to vasopressin-like effect which
can result in hyponatremia
• Drug-drug interactions!

75. Drug interactions
• Drugs that increase carbamazepine levels and/or
toxicity: acetazolamide, cimetidine (both can
cause rapid toxic reactions), clozapine (may act
synergistically to suppress BM), diltiazem, INH,
fluvoxamine, occasionally fluoxetine,
erythromycin, clarithromycin, fluconazole,
itraconazole, ketoconazole, metronidazole,
propoxyphene, verapamil.
• Drugs that decrease carbamazepine levels:
neuroleptics, barbiturates, phenytoin, TCA’s.
• VPA may increase or decrease carbamazepine
levels.

76. • Carbamazepine is a heteroinducer, increasing
its own metabolism and that of many other
drugs, warfarin, methadone, many
psychotropics including antidepressants,
antipsychotics, BZD’s, in addition to
cyclosporine (and other immunosuppressants),
theophylline, etc.

77. Lamotrigine
• Indications similar to other anticonvulsants
• Before med is started: baseline liver function
tests
• Initiation/titration: start with 25 mg daily X 2
weeks then increase to 50mg X 2 weeks then
increase to 100mg and so on- faster titration
has a higher incidence of serious rash
• If the patient stops the med for 5 days or more
have to start at 25mg again!

78. Cardiovascular   
Renal   
Diabetes   
Hepatic   ? 
Hematological    
Thyroid   
Arthritis   
Infectious disorders   
Metabolic   
Disorders Lithium CBZ VPA
Mood stabilizers with medical co-morbidity

79. ANTIPSYCHOTICS

80.  Formulatory decision should be based on cost
when drug of comparable efficacy are
available.
 It is especially important to consider safety
and tolerability along with efficacy and cost.
 Avoid clozapine & ziprasidone in elderly
patients who have corrected/non corrected
QT interval prolongation

81.  Avoid conventional antipsychotics, clozapine
and olanzapine in patients who have diabetes
mellitus, dyslipedimia and/or obesity.
 Avoid ziprasidone , conventional antipsychotics
and clozapine in patients who have congestive
heart failure.
 Quetiapine is the first line recommendation for a
patient with Parkinson’s disease , also consider
low dose olanazapine or clozapine for patients
with Parkinsons

82. Antipsychotics: Typicals
• Are D2 receptor antagonists
• High potency typical antipsychotics bind to the
D2 receptor with high affinity. As a result they
have higher risk of extrapyramidal side effects.
(Examples Haloperidol).

83. • Low potency typical antipsychotics have less
affinity for the D2 receptors but tend to
interact with nondopaminergic receptors
resulting in more cardiotoxic and
anticholinergic adverse effects including
sedation, hypotension. Examples include
chlorpromazine and Thioridazine.

84. Antipsychotics: Atypicals
• The Atypical Antipsychotics - atypical agents
are serotonin-dopamine antagonists (SDAs)
• They are considered atypical in the way they
affect dopamine and serotonin neuro -
transmission.

85. Quetiapine
• Available in a regular tablet form only
• May be associated with weight gain, though less than
seen with olanzapine
• May cause hypertriglyceridemia,
hypercholesterolemia, hyperglycemia (even without
weight gain), however less than olanzapine
• Most likely to cause orthostatic hypotension

86. Olanzapine
• Available in regular tabs, immediate release IM,
rapidly dissolving tab, depot form
• Weight gain (can be as much as 30-50lbs with even
short term use)
• May cause increase triglyceride, cholesterol, and/or
glucose level (even without weight gain)
• May cause hyperprolactinemia (< risperidone)

87. Aripiprazole
• Available in regular tabs, immediate release IM
formulation and depot form
• Unique mechanism of action as a D2 partial agonist
• Low EPS, no QT prolongation, low sedation
• CYP2D6 (fluoxetine and paroxetine), 3A4
(carbamazepine) interactions, so that it is
recommended to adjust the dosing. Could cause
potential intolerability due to akathisia.
• Not associated with weight gain

88. Amisulpride
• Powerful in treatment of +ve symptoms.
• Not approved to has risk of dyslipidemia or
hyperglycemia
• Causing sedation and prolongation of QTc
interval esp. In elderly (dose dependent).
• Use with caution with renal (dose must be
adjusted) or hepatic affection.

89. Risperidone
• Available in regular tabs, IM depot forms and rapidly
dissolving tablet
• Functions more like a typical antipsychotic at doses
greater than 6mg
• Increased extrapyramidal side effects (dose
dependent)
• Most likely atypical to induce hyperprolactinemia
• Weight gain and sedation (dosage dependent)

90. Clozapine
• Available in 1 form- a regular tablet
• Is reserved for treatment resistant patients because of side
effect profile.
• Associated with agranulocytosis (0.5-2%) and therefore
requires weekly blood draws x 6 months, then Q- 2weeks x 6
months)
• Increased risk of seizures (especially if lithium is also on
board)
• Associated with the most sedation, weight gain
• Increased risk of hypertriglyceridemia, hypercholesterolemia,
hyperglycemia, including non-ketotic hyperosmolar coma and
death with and/or without weight gain

91. Ziprasidone
• Available regular tabs and IM immediate
release form
• Clinically significant QT prolongation in
susceptible patients
• May cause hyperprolactinemia (< risperidone)
• No associated weight gain
• Absorption is increased (up to 100%) with
food

92. Asenapine
• Sublingual (no food or liquid for 10 min)
• BID dosing required
• Can start at therapeutic dose
• Low wt gain and metabolic disturbances
• Sedation, somnolence, akathisia
• Not recommended for patients with severe
hepatic impairment
• Be careful with co-administration of (CYP1A2
inhibitor)

93. Leucht S, et al. Lancet 2009; 373(9657):31-41. Slide courtesy of Dick Miyoshi

94. Antipsychotic adverse effects
• Tardive Dyskinesia (TD)-involuntary muscle
movements that may not resolve with drug
discontinuation- risk approx. 5% per year
• Neuroleptic Malignant Syndrome (NMS):
Characterized by severe muscle rigidity, fever, altered
mental status, autonomic instability, elevated WBC,
CPK and lfts. Potentially fatal.
• Extrapyramidal side effects (EPS): Acute dystonia,
Parkinson syndrome, Akathisia
• Mild Cognitive impairment.

95. Agents for EPS
• Anticholinergics such as benztropine,
trihexyphenidyl, diphenhydramine
• Dopamine facilitators such as Amantadine
• Beta-blockers such as propranolol

96. Drug Metabolite t½ (h) CLR and T½
changes in
elderly
CYP enzyme involved in
metabolism (potential
drug interactions)
Geriatric
doses mg
per day
Clozapine Norclozapine, clozapine
N- oxide (very limited
activity)
4-12 CLR
decreased
CYP1A2, CYP2D6,
CYP3A4 (theophylline,
digoxin, warfarin)
50
Risperidone 9 hydroxy risperidone
(active)
20 CLR
decreased
t½ prolonged
CYP2D6 (inhibitor drugs
such as quinidine) 2
Olanzapine 10-N-glucoranide, N-
demethyl-olanzapine
(inactive)
30 CLR
decreased
t½ prolonged
CYP2D6 (inhibitor drugs
such as quinidine) 10
Quetiapine Multiple (main
metabolite is a
sulphoxide, usually
inactive)
6' CLR
decreased
t½ prolonged
CYP3A4 (phenytoin,
Thioridazine)
200

97. COMMON ANTIPSYCHOTIC DRUG INTERACTION IN
THE ELDERLY
Combination Effect
TCAs and conventional
antipsychotics
Raises blood antidepressant
concentrations
SSRIs and clozapine Raises blood clozapine concentrations
Risperidone and clozapine Raises blood clozapine concentration
Smoking Lower blood antipsychotic concentration
Cimetidine Lower blood antipsychotic concentration
Anticholinergic drugs Additive memory and delirious effects
Anticonvulsant, antihypertensive
and sedative drugs
Additive sedative and delirious effects

98. ANTI-DEMENTICS

99. • Cholinesterase inhibitors-mild to moderate
dementia
• Memantine HCl in moderate to severe demantia
– Prescription only for-
• probable Alzheimer’s disease
• duration of illness > 6months
• MMSE > 10
– 3 phase response evaluation-
• Early (2 wk)-assess tolerance & side effects
• Late (3 mth)-assess cognition
• Continued (6 mth)- assess disease state

100. –Stop treatment if
• Early evaluation shows poor tolerance or
compliance
• Deterioration continues at pretreatment rate
after 3-6 month of medication
• On maintenance doses, accelerated
deterioration

101. Drugs useful for reducing the signs of
dementia
Drug Dose
Donepezil 5-20 mg daily
Rivastigmine 1.5-6 mg b.i.d.
Galantamine 4-12 mg b.i.d.
Memantine 5-20 mg daily

102. Assiut in 2014 winter