# Polypharmacy and Psychotropic Deprescribing in the Elderly

## Introduction

Polypharmacy, commonly defined as the concurrent use of five or more medications, is prevalent among older adults and is particularly concerning with psychotropic medications. Older adults are more susceptible to adverse drug effects due to altered pharmacokinetics, pharmacodynamic sensitivity, and medical comorbidities. **Deprescribing** is the systematic process of identifying and discontinuing medications when the potential harms outweigh the benefits, and it is an essential clinical skill in geriatric psychiatry.

## The Problem of Polypharmacy

### Scope

Over 30% of adults aged 65+ take five or more medications. Psychotropic polypharmacy (two or more psychotropics) affects a substantial proportion of older psychiatric patients. Nursing home residents are at highest risk, with average medication counts of 7-10 drugs.

### Consequences

**Adverse drug reactions** increase exponentially with the number of medications. **Drug-drug interactions**: CYP450 inhibition and induction, pharmacodynamic interactions. **Anticholinergic burden**: cumulative cognitive impairment, falls, delirium, constipation, urinary retention. **Falls and fractures**: sedation, orthostatic hypotension, impaired balance. **Cognitive impairment**: benzodiazepines, anticholinergics, and opioids are common culprits. **Non-adherence**: complex regimens reduce adherence. **Hospitalization**: adverse drug events account for up to 30% of hospital admissions in older adults.

![Cascade of risks associated with psychotropic polypharmacy in elderly patients](images/polypharmacy-risk-cascade.png)

## High-Risk Psychotropic Medications in the Elderly

### Beers Criteria Highlights

The **American Geriatrics Society Beers Criteria** identify medications that are potentially inappropriate in older adults:

| Drug Class | Examples | Primary Risks in Elderly | Beers Recommendation |
|-----------|----------|------------------------|---------------------|
| Benzodiazepines | Diazepam, alprazolam, lorazepam | Falls, fractures, cognitive impairment, delirium | Avoid for insomnia/agitation/delirium |
| Z-drugs | Zolpidem, zaleplon | Falls, complex sleep behaviors | Avoid; similar risk to benzodiazepines |
| Tertiary amine TCAs | Amitriptyline, imipramine | High anticholinergic burden, cardiac conduction | Avoid; use secondary amines if TCA needed |
| First-generation antipsychotics | Haloperidol, chlorpromazine | EPS, anticholinergic effects, falls | Avoid except for schizophrenia/bipolar |
| Anticholinergics | Diphenhydramine, hydroxyzine, oxybutynin | Cognitive impairment, delirium, urinary retention | Avoid |
| Meperidine | Demerol | Neurotoxic metabolite (normeperidine); seizures | Avoid |

**Benzodiazepines**: increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents; avoid for insomnia, agitation, or delirium. **Non-benzodiazepine hypnotics** (zolpidem, zaleplon): similar fall risk without proven superiority. **Tricyclic antidepressants** (particularly tertiary amines: amitriptyline, imipramine): high anticholinergic burden, cardiac conduction effects. **First-generation antipsychotics**: high EPS risk, anticholinergic effects. **Anticholinergic drugs**: diphenhydramine, hydroxyzine, benztropine, oxybutynin.

### STOPP/START Criteria

**STOPP** (Screening Tool of Older Persons' Prescriptions): identifies potentially inappropriate prescriptions. **START** (Screening Tool to Alert to Right Treatment): identifies potential prescribing omissions. Complementary to Beers Criteria; widely used in European and international settings.

### Anticholinergic Burden Scales

**Anticholinergic Cognitive Burden (ACB) Scale**: rates medications on a scale of 1-3 based on anticholinergic potency. Cumulative anticholinergic burden correlates with cognitive decline, functional impairment, and mortality. Total ACB score of 3 or more is associated with significantly increased risk.

## Pharmacokinetic Changes with Aging

**Decreased hepatic metabolism**: reduced liver mass, hepatic blood flow, and CYP enzyme activity (particularly Phase I reactions) **Reduced renal clearance**: GFR declines approximately 1 mL/min/year after age 40; affects lithium, gabapentin, and active metabolites. **Increased body fat**: longer half-life for lipophilic drugs (diazepam, chlorpromazine) **Decreased albumin**: increased free fraction of highly protein-bound drugs (valproate, phenytoin) **Increased CNS sensitivity**: enhanced pharmacodynamic response to psychotropics, particularly sedatives.

## The Deprescribing Process

### Step 1: Review All Medications

Compile a complete list including over-the-counter medications, supplements, and as-needed drugs. Identify the original indication for each medication. Assess current appropriateness using Beers Criteria and clinical judgment.

### Step 2: Assess Risk-Benefit for Each Drug

Is the original indication still present? Has the medication been effective? Do the risks now outweigh the benefits given the patient's age, frailty, and life expectancy? Could this medication be causing current symptoms (e.g., is a benzodiazepine causing falls)?

### Step 3: Prioritize Medications for Discontinuation

Highest priority: medications causing current harm (falls, confusion, sedation) Medications without a clear indication. Medications with marginal benefit relative to risk. Medications prescribed for conditions that have resolved.

### Step 4: Plan and Execute Gradual Tapering

Most psychotropics should be **tapered gradually** rather than stopped abruptly. Benzodiazepines: reduce by 10-25% every 1-2 weeks; slower tapers for long-term use. Antidepressants: taper over 4-8 weeks to avoid discontinuation syndrome. Antipsychotics: reduce by 25-50% every 2-4 weeks with behavioral monitoring.

### Step 5: Monitor and Follow Up

Schedule follow-up within 1-4 weeks of each dose change. Monitor for withdrawal symptoms, return of original symptoms, and overall function. Be prepared to re-institute medication if clinically necessary.

![Five-step deprescribing process flowchart for psychotropic medications](images/deprescribing-process-flowchart.png)

## Barriers to Deprescribing

**Prescriber inertia**: reluctance to change another clinician's prescription. **Patient and family resistance**: fear of symptom recurrence. **Prescribing cascades**: a new drug prescribed to treat side effects of an existing drug. **Lack of evidence**: few RCTs specifically studying deprescribing outcomes. **Fragmented care**: multiple prescribers without coordination.

## Specific Deprescribing Guidance

### Benzodiazepines

Taper slowly (10-25% reduction every 2-4 weeks for chronic use) Switch from short-acting to long-acting formulation to reduce interdose withdrawal. Offer CBT for insomnia (CBT-I) as a replacement strategy. Education about rebound insomnia and anxiety being temporary.

### Antipsychotics in Dementia

Attempt taper after 3-6 months of behavioral stability. Multiple RCTs support that most patients can be successfully withdrawn. Monitor closely for behavioral recurrence in the first 2-4 weeks.

### Long-Term Antidepressants

After remission of a first episode, consider tapering after 6-12 months. With recurrent depression, weigh the risk of relapse against adverse effects. Gradual taper over 4 or more weeks; monitor for relapse.

![Specific tapering schedules for common psychotropic medication classes in elderly patients](images/elderly-psychotropic-tapering.png)

## Key Clinical Pearls

Every new symptom in an older adult should prompt a medication review before adding a new drug. The prescribing cascade is one of the most common drivers of polypharmacy: identify and interrupt it. Deprescribing requires the same level of clinical skill and follow-up as prescribing. Shared decision-making with patients and families is essential; address fears about symptom recurrence. "Start low, go slow, but also know when to let go".

## References

1. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. *J Am Geriatr Soc*. 2023;71(7):2052-2081.
2. Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: the process of deprescribing. *JAMA Intern Med*. 2015;175(5):827-834.
3. Reeve E, Shakib S, Hendrix I, Roberts MS, Wiese MD. Review of deprescribing processes and development of an evidence-based, patient-centred deprescribing process. *Br J Clin Pharmacol*. 2014;78(4):738-747.
4. Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: a clinical review. *Clin Interv Aging*. 2009;4:225-233.