Psychopharmacological Treatment of Geriatric Disorders
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Transcript Psychopharmacological Treatment of Geriatric Disorders
Organization of inpatient care for
Geriatric Mental Health Care
SHIV GAUTAM
MD(psych), DPM, FAMS
Sr.Professor, HOD & Supdt.
Psychiatric Centre Jaipur
Addl.Principal SMS Medical College Jaipur
Aging Physiology
• Individuals become more dissimilar as they
grow.
• Abrupt decline in any system is always due to
disease and not to normal aging.
• Normal aging can be attenuated by
modification of risk factors.
• In the absence of disease decline in
homeostatic reserve causes no symptoms and
imposes few restrictions in activities of daily
living regardless of age.
Aging Pathology
• Multiple Pathology
– Cataracts, deafness, degenerative joint
diseases, like osteoarthritis or osteoporosis,
varicose veins are all conditions which are
likely to develop slowly and to progress.
– Cancer, pernicious anaemia, thyrotoxicosis,
myxoedema common due to deterioration
of immune mechanisms.
– Obesity, diabetes, depression and
dementia frequently seen
Under reporting of illness
• Callous Attitude Towards
Health
• Attitude of the Relatives
Barriers to Obtaining
Proper History
• Mental Confusion
• Deafness
• Concentration
• Co-operation
• Idiosyncrasis
Neuro-Psychiatric Disorders
• Cerebrovascular Diseases
• Depressive and other Psychiatric
Disorders
• Cognitive Impairment and Dementia
• Neurodegenerative Disorders
• Infections of the Central Nervous
System, Sleep Disorders and Coma.
Laboratory Evaluation and Other
Investigations
• Routine Haematological Tests Complete Blood cell count
Platelets count
Prothrombin time
Blood glucose level
Hepatic Panel
Serum Electrolytes
Renal Panel
Routine Diagnostic Tests • Lipid Profile, Blood sugar fasting, Electrocardiogram,
Chest radiograph,
• Optional – EEG, CT Scan, MRI
Facilities for an inpatients Geriatric
Mental Health Care
• Entrance with ramp and
wheel chair
• Adequate OPD space
with waiting facilities
• Consultation chambers
for mental health team
(Psychiatrists, Clinical
Psychologist,
Psychiatric Social
worker)
• Nursing Station and
Drug dispensing
• Inpatient wards with
attendant facility
• Semi ICU
• Lab investigations
facilities
• Recreation room
• Rehabilitation activities
• Storage and
Documentation space
INTERDISCIPLINARY TEAM
CONSULTATION-LIASION
• Medical internist
Gynaecologist
• Ophthalmologist
Orthopaedician
• Physiotherapist
Dietician
• Yoga trainer
Age related changes in the Central
Nervous System
Gross brain atrophy
Ventricular enlargement
Selective regional neuronal loss
Remodeling of dendrite, axons &
synapses
Appearance of intraneuronal
lipofuschin
Selective regional decrease in
neurotransmitter & neuropeptides.
Contd...........
Selective modification of
neurotransmitter metabolism
Possible dysregulation of gaseous
neurotransmitter metabolism
Glucocorticoid neurotoxicity
Changes in receptors
Changes in neurotrophins
Changes in signal transduction
…contd.
Impairment of calcium homeostasis
Possible changes in cell cycle regulations
(eg, cyclins)
Possible changes in extra cellular matrix
proteins (eg. Laminin, proteoglycans)
Possible regional decline in cerebral blood
flow
Possible regional decline in metabolic rate
Appearance of senile plaque &
neurofibrillary tangle
PHARMACODYNAMICS AND AGING
Neurotransmitter Pharmacodynamic changes
with aging
Dopaminergic system
Dopamine D2 receptor in the striatum
Cholinergic system
Choline acetyl transferase
Cholinergic cell numbers
Contd...........
Contd...........
Adrenargic system
cAMP production in response to beta-agonists
Beta – adrenoceptor number
Beta – receptor affinity
Alpha 2 – adrenoceptor responsiveness
Gabaminergic system
Psychomotor performance in response to
benzodiazepines
? Post – synaptic receptor response to GABA.
PHARMACOKINTIC CHANGES WITH AGING
Absorption
Metabolism
gastric pH
Hepatic mass
(Delayed) gastric emptying
Hepatic blood flow
Splanchnic blood flow
Intestinal motility
Phase I Metabolism
(unchanged) phase II metabolism
Distribution
Elimination
Body Fat
Creatinine clearance
Total body water
Glomerular filtration rate
Albumin
Tubular secretion
Alpha1 acid glycoprotein
Creatinine production
Points to remember before
prescribing medication in elderly
Magnitude of effect (clinical response) = Pharmacodynamics x
Pharmacokinetics x biological variance
In elderly medical complication of pharmacotherapy alone
constitute a highly significant treatable health problem.
Adverse reaction to drugs of all types is seven times higher
in those aged 70 to 79 years, than in those 20 to 29 years old.
Non compliance with therapy is a major problem for
psychiatric patients, and this dilemma is exacerbated with
age.
Age related health problems combines with physiological
changes to increase the probability of adverse effect from
medication which in turn increase the likelihood of non
compliance.
Complexities of medication regimens are further complicated
by communication difficulties arising from impaired hearing,
cognitive impairment, language & cultural difficulties.
Psychopharmacological Treatment of
Geriatric Disorders
Q.
Q.
Q.
Q.
Q.
Q.
The psychiatrist of an 87 year old patient suffering from
heart disease, arthritis and depression must ask a number
of questions to himself.
What is the best treatment - Pharmacotherapy?
Psychotherapy? E.C.T.?
If pharmacotherapy, what is the most appropriate drug?
Balancing the adverse effect and efficacy. What is the best
dosage?
How soon will the patient’s symptom decrease?
If the drug is effective. How long will the treatment last?
If the drug is ineffective how long should the wait before
changing the treatment?
GERIATRIC MANIA
Risk of Mania decline in late life, nonetheless mania
and hypomania affect 5-10% of psychiatric patients.
Established mood stabilizers
Lithium salts
Clozapine,
Valproate
Olanzapine
Carbamazepine
Magnesium salt
Calcium channel blockers
Newer Anticonvulsants
E.C.T.
Lamotrigine,
Gabapentin
Topiramate,
Tigabine
Putative Mood stabilizes"
L. Thyroxine
Phosphatidyl choline
Progesterone
Omega 3 fatty acid
Antidepressants in
old age depression
• Cumulative incidence of depression in
people aged upto 70 years is 26.95% for
men & 42.5% for women, still most of the
drug trials exclude elderly subjects.
• In addition, most of the drug trials also
exclude subjects with medical comorbidity,
which is a rule rather than exception. Hence
the results of drug trials done in young adults
can't be generalized to elderly.
…Antidepressants in old age depression contd.
• Prior to 1995, there were occasional
studies which evaluated the use of
antidepressants in elderly. But fortunately
in the last 10 years many studies have
evaluated the use of antidepressants in
the elderly.
• These studies can be broadly classified
as:
• Noncomparative studies
• comparative studies using either placebo or
another antidepressant or both and
• meta-analyses of the above studies.
Antidepressant Drugs and Dosages Preferred for
Use in the Elderly
Drugs
Geriatric dosage
(mg per day)
Starting
dosage
Side Effects
Maintenance Sedation
dosage
Agitation
Anticholinergic
effects
Orthostatic
hypotension
Low
Low
Low
Low
Low
Tricyclic antidepressants
Desipramine
25
50 to 150
Low
Nortriptyline
10 to 25
40 to 75
Moderate
Selective serotonin reuptake inhibtiors
Citalopram
20
20 to 40
Low
Low
-
-
Fluvoxamine
50
50 to 200
Low
Low
-
-
Paroxetine
10
20 to 30
Low
Low
-
-
Sertraline
25 to 50
50 to 150
Low
Low
-
-
Bupropion
100
100 to 400
-
Moderate
-
Low
Nefazodone
100
100 to 600
Moderate
--
Low
Low
Trazodone
25 to 50
50 to 300
High
-
Low
Moderate
Venlafaxine
75
75 to 350
Low
Low
Low
Low
Miscellaneous
Anticonvulsants in Depression with medical comorbidity
Disorders
Lithium
CBZ
VPA
Cardiovascular
Renal
Diabetes
Hepatic
?
Hematological
Thyroid
Arthritis
Infectious disorders
Metabolic
Psychotic agitation in the elderly with mania
Initial treatment
Haloperidol 0.25 to 0.5 mg IM or PO
After one hour, administer lorazepam 0.5mg IM or PO
Stabilization
Repeat alternating doses every hour until calm
Monitor carefully to avoid over sedation
Alternative regimen if extra pyramidal symptoms develop
Atypical antipsychitic riseperidone (0.5mg), or olanzapine (2.5
- 5 mg)
Avoid chlorpromazine and thioridazine due
anticholinergic and hypotensive side effects.
to
Chronic medication
Daily dose of medication is determined by adding the total
dose of each medication required to calm the patient and
dividing it equally throughout the day.
their
Adjunctive antipsychotic medication
Risperidone
Daily divided doses of .5 to 3mg
Monitor patient carefully for orthostatic hypotension and EPS as dose
is increased
Olanzapine
Daily doses of 2.5 to 10 mg /day’
Transient elevation in liver enzyme have been reported
Risepeidone plus olanzapine
Observe for increased agitation or other manic symptom because of
breakthrough mania with risperidone.
Clozapine
Reserved for patients who are intolerant of risperidone and olanzapine,
Daily doses start at 12.5mg, increase to 50mg
If history of seizure disorder should be maintained on an
anticonvulsant
Monitor for orthostatic hypotension and weekly complete blood count
to assess for evidence of bone marrow toxicity
ATYPICAL ANTIPSYCHOTICS IN THE
ELDERLY
Drug
Clozapine
Metabolite
Norclozapine, clozapine
N- oxide (very limited
activity)
t½ (h) CLR and T½
changes in
elderly
4-12 CLR
decreased
Risperidone 9 hydroxy risperidone
(active)
20
Olanzapine 10-N-glucoranide, Ndemethyl-olanzapine
(inactive)
30
Quetiapine
6'
Multiple (main
metabolite is a
sulphoxide, usually
inactive)
CYP enzyme involved in Geriatric
metabolism (potential doses mg
drug interactions)
per day
CYP1A2, CYP2D6,
CYP3A4 (theophylline,
digoxin, warfarin)
50
CLR
CYP2D6 (inhibitor drugs
decreased
such as quinidine)
t½ prolonged
2
CLR
CYP2D6 (inhibitor drugs
decreased
such as quinidine)
t½ prolonged
10
CLR
CYP3A4 (phenytoin,
decreased
Thioridazine)
t½ prolonged
200
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
Expert consensus guidelines
SPECIAL ISSUE IN USING ANTIPSYCHOTICS IN
THE ELDERLY
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 low and mid-potency conventional
antipsychotics as well as clozapine &
ziprasidone in elderly patients who have
corrected QTc interval prolongation.
…Expert consensus guidelines
DISEASE DRUG INTERACTION
Avoid low & mid potency conventional antipsychotics,
clozapine and olanzapine in patients who have
diabetes mellitus, dyslipedimia and or obesity.
Avoid ziprasidone, low and mid potency conventional
antipsychotics and clozapine in patients who have a
prolonged QTc interval or 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
Avoid high dose of risperidone in patients with
Parkinson’s disease
Management of Cognitive
symptoms-Dementia
• Cholinesterase inhibitors-mild to moderate
dementia (Cummings et al., 2004).
– 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
…Management of Cognitive symptoms contd.
– Stop treatment if• Early evaluation-poor tolerance or
compliance
• Deterioration continues at pretreatment rate
after 3-6 month of medication
• On maintenance doses, accelerated
deterioration
Drugs useful for reducing the
signs of dementia
Drug
Dose
Donepezil
5-10 mg daily
Rivastigmine
1.5-6 mg b.i.d.
Galantamine
4-12 mg b.i.d.
Memantine
5-20 mg daily