Transcript Psychiatric Polypharmacy, Etiology and Potential Consequences

Psychiatric
Polypharmacy,
Etiology and Potential
Consequences
Sonali Sarkar MD, MPH,
DrPH
Acknowledgement
• United States Army Institute of
Surgical Research (USAISR)
• Oak Ridge Associated Universities
(ORAU)
• University of Texas Health Science
Center at San Antonio (UTHSCSA)
Presentation Overview
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Definition of psychiatric polypharmacy
Introduction
Methods
Epidemiology
Etiologic factors
Potential consequences
Harmful polypharmacy with examples
Beneficial polypharmacy with examples
Practice guidelines
Psychiatric Polypharmacy
• Two or more drugs used in the treatment of a
psychiatric condition [1]
• Referred to as [2-4]
- Potentially inappropriate medication (PIM)
- Antipsychotic polypharmacy (APP)
- Hyper-pharmacotherapy
- Co-medication / co-prescription
- Multiple medication use
Introduction
• Psychiatric polypharmacy is a major public
health problem
• Rising trend of polypharmacy in the U.S is
growing at an alarming rate [5]
• Polypharmacy trend also observed in other
parts of the world [5]
Methods
• Review of online databases (PubMed, Medline,
EBSCO, Psychinfo) was conducted
• Time period: 2000-2016
• Population: Adults + child/ adolescents
• Key words were searched using “And” “Or”
- Search terms: psychiatry, polypharmacy,
multiple medication, epidemiology, prevalence,
antidepressant, antipsychotic, adverse reaction,
side-effect, interaction, practice, guidelines,
recommendation
Methods
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Search yielded approx. 1000 articles
Initial review: included 289 articles
Articles were reviewed one by one
Final review: included 250 articles that
were recent & relevant to the topic
Epidemiology
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Prevalence is increasing globally [5]
Common in patients with schizophrenia [6]
Noted in 30-50% of adult schizophrenics [7,8]
Prevalence of polypharmacy with second gen
antipsychotics (SGA) is rising (3.9-50%) [9]
• Commonly co-prescribed SGA are risperidal
and olanzapine [10]
Epidemiology
• Polypharmacy is noted not only with
antipsychotics but also with antidepressants,
mood stabilizers, and sedative-hypnotics [11]
• National trends in polypharmacy in an office
setting indicate common drugs prescribed [12]
• Antidepressants (61.7%)
• Antidepressants + sedative hypnotics (23.1%)
• Antidepressants + antipsychotics (12.9%)
• Antidepressants + antidepressants (12.6%)
Epidemiology
• Noted in adults with psychosis, borderline
personality d/o, affective and mood d/o[13-14]
• In adults with affective/bipolar disorder,
prevalence rate of one or more antidepressant
or antipsychotic is approximately 36-85%
[15,16]
• Silent epidemic of polypharmacy is seen not
only in adults but also in children &
adolescents [17]
Epidemiology
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Among youths, prevalence rate is 8-12% [17]
Combinations of SGA+SGA are common [18]
Aripiprazole/quetiapine (23% and 17%)
Risperidal/quetiapine (18% and 15%)
Aripiprazole/ risperidone (17% and 11%)
Risperidal/olanzapine (5% and 6%)
Quetiapine/olanzapine (4% and 7%)
Epidemiology
• In youths, antidepressants are co-prescribed
with stimulants & antipsychotics [19]
• Youth antidepressant (SSRIs) prescription
prevalence rate is approximately 2-5% [20]
• In youth ADHD, psychostimulant (Ritalin)
prescription rate with antipsychotic is 3.9% [21]
Polypharmacy Etiology
• Rationale for polypharmacy is not clear
• Prior studies are limited as they are [22-24]
-Observational vs. interventional
-Lack tools to assess polypharmacy efficacy
-Rely on prescriber autonomy
-Poor response rate
-Lack power: small sample size
-Inadequate control of confounders
Polypharmacy Etiology
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Demographic factors
Psychiatric condition
Comorbidity
Substance abuse
Prescribing practice
Patient determinants
Demographic factors (adult)
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Age (18-25 yrs) [8]
Age advancement [8]
Gender: Male (majority)/female gender [25,26]
Low education, poor SES, Medicaid/public
insurance [26, 27]
Race: mixed findings reported
AA: cumulative higher dose, older drugs &
depot formulations [28, 29]
CATIE trial: Coprescription less likely in AA [25]
No differences by race/ethnicity [30,31]
Demographic factors (youth)
Among children & adolescents [32, 33]
• Age children (13-15 yrs)
• Male gender
• Caucasian race
• Low socio-economic status
• Medicaid/public insurance
• Disability status
• Child custody outside/ foster care
Psychiatric Condition (adult)
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Schizophrenia/psychosis [8]
Treatment refractory/difficult to treat [35]
Negative symptoms/depressive d/o [36]
Violence, hostility, suicidality [36]
Severity of condition[35]
Inpatient status (majority)/ outpatient [12]
Longer hospitalization/shorter follow up[12,35]
Psychiatric Condition (youth)
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Child clinical correlates [21, 37]
Autism spectrum disorder (ASD)
Attention deficit hyperactivity d/o (ADHD)
Conduct d/o (CD)
Oppositional defiant d/o (ODD)
Adolescent clinical correlates [39]
Schizophrenia spectrum disorder
Mood d/o, Bipolar illness
Anxiety d/o, CD/ODD
Comorbidity
• Adult: obesity, dyslipidemia, metabolic
syndrome, somatic pain, dementia, MR,
Alzheimer’s disease, personality d/o [38]
• Pediatric: enuresis, encopresis, neurological
d/o, motor tics, developmental d/o, obsessive
compulsive personality d/o [37]
• Higher comorbidity score/index is associated
with polypharmacy [32]
Substance abuse
• Substance abuse: predictor of polypharmacy [40]
• Polysubstance abuse: nicotine, alcohol, drugs
(marijuana/cocaine) is prevalent [40]
• Youth substance abuse: h/o abuse, MDD, Mania,
CD, ADHD [41]
• Youth ADHD: Antipsychotic + stimulants [40,41]
• Intoxication/withdrawal need Rx with CNS drugs
• Benzodiazepines + antipsychotics [42]
Prescribing practice
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Perception, attitude, prescriber knowledge[43]
Child psychiatrists prescribe more meds [32,34]
Prescribers’ deviate from routine algorithm[23]
Lack of adequate monotherapy trials [23,24]
Polypharmacy noted at treatment initiation
phase: explains the rising prevalence [24]
• Prescribers are under pressure, focus on drug
Rx instead of global improvement [44]
• Prescriber bias: qualitative/quantitative diff. in
prescribing practice to minority pt. [28,29]
Patient determinants
• Attitude, cultural beliefs, family influence,
racial/ethnic diff: polypharmacy [45]
• Behaviors: doctor shopping, multiple
providers, request for meds, early med refill,
prescription drug abuse [46]
• Health disparities, indiv variablity in genetic
polymorphisms, drug metabolism,
pharmacogenetics/pharmacokinetics:
polypharmacy determinants [47]
Patient determinants
• In youths, parental/child perception, parental
request for meds, attitude & belief towards
psychiatric Rx [48]
• Youth violent behavior, impulsivity, aberrant
behaviors are associated with polypharmacy
[21, 32, 33]
Consequences
• Adverse effects: weight gain, sexual
dysfunction, anticholinergic side-effect [49]
• SGA’s : metabolic syndrome, hyperlipidemia,
type 2 D.M, glucose intolerance [50]
• In youth: Rx emergent type 2 D.M w SGA [51]
• Drug to drug interactions: effect on Cyt P450
• Elderly: cognitive impairment, falls, fracture [52]
• Cumulative toxicity, mortality & morbidity [53]
• Rx complexity: non-compliance/adherence [54]
• Mental health cost/economic burden [55]
Beneficial Polypharmacy
• Concept: Synergistic action of drugs w diff
mechanism of action on multiple
neurochemical pathway [56]
• Improve therapeutic outcome & clinical s/o [56]
- Ex:Venlafaxine(mood d/o) + amitryptiline(pain)
- Ac. Psychosis: FGA(haldol) + SGA (risperdal)
• Approach is used to target two diff psych cond
- Psychosis (risperdal) + Anxiety (quetiapine)
- Depression (SSRI) + Seizure (gabapentin)
Beneficial Polypharmacy
• Affective d/o (rec. cyclic manic episodes)
-Lithium (add on) + SSRI/Bupropion
(depression) [57, 58]
• Bipolar d/o: Lithium (maintenance) +
anticonvulsants (divalproate, carbamazepine,
lamotrigine) [59]
• Lithium as add on: clinical efficacy,
antisuicidal effect (decreased
aggression/impulsivity) [60]
Beneficial Polypharmacy
• Rx resistant depression: drugs targeting
inhibition (5HT) + NE receptors [61]
• SSRI (prozac) + NE uptake inhibitor
(desipramine) is effective than monotherapy
• Combination w 3 diff antidepressants was
more effective than Fluoxetine monotherapy
[62, 63]
- Mirtazapine + SSRI (Paxil)
- Mirtazapine + Venlafaxine
- Mirtazapine + Bupropion
Beneficial polypharmacy
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Newer antidepressants(multitarget agents) [64]
Fewer & milder side-effects
Provide complimentary strategy for psych Rx
To reduce risk of EPS, anticholinergic effects,
Proven beneficial in ameliorating symptom[65]
Thus, rational polypharmacy improves clinical
outcome & GAF score.
Harmful Polypharmacy
• Some drug combinations: none to low clinical
response; proven futile/harmful [66]
- Ex: SGA (risperdal) + SGA (clozapine) [67]
• RCT: Combining Meds to Enhance Depression
Outcomes (CO-MED) study= No diff in
remission/response rate in 12 wks in grps [68]
- Escitalopram + Placebo
- Escitalopram + Bupropion
- Venlafaxine + Mirtazapine
Harmful Polypharmacy
• Sudden cardiac death: QT prolongation
(Torsade de Pointes) with polypharmacy [69]
- Haldol/Thorazine + Ziprasidone/quetiapine
- Need cardiac eval, EKG, monitoring of vitals
• Pediatric SGA for behavioral d/o in absence of
evidence based indication= med side-effect,
wt. gain, metabolic syndrome [70]
Practice Guidelines
• Prior studies have listed in detail [71-75]
• These include:
• Initiate polypharmacy only when monotherapy
fails.
• Synergism in drugs mechanism of action
• FGA + SGA block dopaminergic+serotonergic
• Used in Ac. Psychosis, agitation
- Ex: Haldol (FGA) in pt. w risperdal (SGA)
Practice guideline
• Specific targeting of Rx emergent symptom
clusters
- Ex: Rx emergent anxiety, positive/neg s/o of
schizophrenia benefit from add on SGA/benzo
• Augmentation in Rx refractory psych cond
- Sec antipsychotic can be added if failed
antipsychotic trial/suboptimal response w
clozapine
• Noncompliance: Maintenance (Inj.depot)
continued + antipsychotics to prevent relapse
Practice guidelines
• Continue antipsychotic combinations if
therapeutic efficacy & safety is noted
- Ex: Beneficial neurocog. effects noted with
SGA (olanzapine + risperdal) vs haldol alone
• Personality d/o (OCD) in schizophrenia can be
Rx w SGA
- Aripiprazole/amisulpride + SGA (5HT2)
• Diff. class of antidepressants (synergistic
effect): Refractory depression
Practice guideline
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For affective/mood d/o follow these steps
If partial benefit noted; side-effect is mild, then
Increase the dose of first medication
Switch to another class of antidepressant
Augment the first med w second
antidepressant w diff mech of action (improves
clinical outcome w no increase in side-effect)
Practice guidelines
• Multimodal Rx approach w 2 or 3 drugs for Rx
resistance (MDD/Bipolar d/o)
- Ex: SSRIs can be used w augmentation agents
that have synergistic action
- Anticonvulsants (valproate/lamotrigine)
- Lithium (mood stabilizer)
- Atypical antipsychotics
- Melatonin, Buspirone, Thyroxine
Practice guidelines
• Adjunct meds (antiparkinsonian, sedativehypnotics, anticholinergic drugs) + FGA
- To reduce EPS symptoms and side-effects
- Ex: Haldol + ativan + benadryl
• Child Psychiatrists’ need to obtain detailed
h/o, diff bet. behav & psych d/o before
prescribing meds in youths.
Questions?
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