Geriatric Psychiatry: Polypharmacy, Deprescribing, and Age-Specific Clinical Challenges

1. Pharmacokinetic and Pharmacodynamic Changes with Aging

Absorption and Distribution

Absorption is generally preserved in older adults, though reduced gastric acid may impair ionizable drugs. More significant is altered body composition: aging increases total body fat (18–36% at age 20 to 30–40% at age 70+) and decreases total body water. Fat-soluble drugs (benzodiazepines, antipsychotics) accumulate in fat stores, producing longer half-lives and increased risk of toxicity. Protein binding changes also occur: reduced serum albumin (particularly in frail, malnourished elders) leads to increased free (unbound, active) drug fraction.

Hepatic Metabolism

Hepatic blood flow decreases ~40% with age, and cytochrome P450 enzymatic activity is reduced 20–40% overall (though CYP2D6 and CYP3A4 are variably affected). Phase I metabolism (oxidation, reduction, hydrolysis) is most affected; Phase II (glucuronidation, sulfation) is relatively preserved. This means drugs metabolized via CYP450 accumulate disproportionately.

Renal Clearance: The Most Critical Change

Renal function declines predictably with age: glomerular filtration rate (GFR) decreases ~1 mL/min/year after age 30. A 80-year-old has ~50% of the renal function of a 30-year-old. This matters profoundly: lithium, many antidepressants (fluoxetine metabolites, citalopram), anticonvulsants (valproate), and other medications are renally cleared. Serum creatinine may be normal despite significantly reduced GFR (due to decreased muscle mass producing less creatinine). Estimated GFR (eGFR, using Cockcroft-Gault or MDRD equation) is far more accurate than serum creatinine alone. Dose adjustments for renal impairment are essential.

Pharmacodynamic Changes: Increased Sensitivity

Beyond metabolism changes, older brains are hypersensitive to psychotropic drugs. CNS sensitivity to sedatives, antipsychotics, and anticholinergics increases dramatically. The blood-brain barrier becomes more permeable; altered receptor sensitivity and neurotransmitter abnormalities increase vulnerability. This means "normal" doses often produce excessive effects. The aphorism "start low, go slow" is not just caution — it is pharmacologically sound medicine.

2. The American Geriatrics Society Beers Criteria (2023 Update)

The Beers Criteria provide evidence-based guidance on medications to avoid or use with caution in adults age 65+. The criteria are not absolute contraindications but rather expert consensus on inappropriate use patterns associated with preventable harm.

Psychiatric Medications to AVOID in Older Adults

Benzodiazepines: Avoid in all older adults. Increase risk of cognitive impairment, delirium, falls, fractures, motor vehicle accidents. Alternatives: SSRIs for anxiety, buspirone, psychotherapy. If discontinuing chronic benzodiazepines, taper slowly (10% per week minimum).

Anticholinergic Medications: Avoid use of anticholinergics. Tricyclic antidepressants (amitriptyline, nortriptyline, doxepin) have strong anticholinergic effects; anticholinergic antiparkinson drugs increase confusion and urinary retention. Anticholinergic burden (cumulative effect of multiple anticholinergic medications) is associated with cognitive decline and delirium. Anticholinergic Cognitive Burden Scale quantifies risk.

Antipsychotics in Dementia: Avoid antipsychotics in older adults with dementia unless for specific psychotic symptoms or severe agitation unresponsive to behavioral intervention. Black box warning: increased mortality in dementia patients treated with antipsychotics (primarily cardiovascular and infectious causes). When necessary, use lowest doses for shortest duration.

Sedating Antidepressants: Tricyclics (amitriptyline) are avoided due to anticholinergic effects + sedation. Mirtazapine, though less anticholinergic, causes significant weight gain and sedation in elderly.

Psychiatric Medications to USE WITH CAUTION

SSRIs: Generally preferred for depression and anxiety. BUT: risk of hyponatremia (SIADH) particularly in first 2 weeks; monitor sodium, especially if symptomatic hyponatremia develops. Citalopram/escitalopram: FDA recommends maximum dose 20 mg/day (citalopram) or 10 mg/day (escitalopram) in age 60+ due to QT prolongation risk at higher doses.

Lithium: Narrow therapeutic window becomes narrower with age; renal function decline increases accumulation risk. Therapeutic level in elderly should be 0.4–0.6 mEq/L (vs. 0.6–0.8 in younger adults). Monitor closely; NSAIDs increase lithium levels. Dehydration during acute illness rapidly produces toxicity.

3. Deprescribing: Systematic Medication Reduction

Deprescribing is the systematic, planned dose reduction or discontinuation of medications that are no longer beneficial or may be causing harm. It is distinct from simply stopping medications; rather, it is evidence-based reduction following a structured protocol.

STOPP/START Criteria

The STOPP/START criteria (Screening Tool of Older Persons' potentially inappropriate Prescriptions / Screening Tool to Alert to Right Treatment) provide practical algorithms for identifying potentially inappropriate medications and recommending alternatives. Examples:

• STOPP: Benzodiazepines (avoid) → START: Buspiron for anxiety
• STOPP: Amitriptyline (anticholinergic) → START: Citalopram or sertraline
• STOPP: Antipsychotic in dementia (except for specific psychotic symptoms) → START: Behavioral approaches, environmental modification
• STOPP: Long-term NSAIDs (GI bleeding risk) → START: Acetaminophen, topical NSAIDs, non-pharmacological pain management

Deprescribing Protocol Steps

Step 1: Medication Reconciliation. Obtain complete list of all medications, including OTC and supplements. Identify potentially inappropriate medications per Beers Criteria and STOPP/START.

Step 2: Assess Current Appropriateness. For each medication, ask: (1) Is there an indication? (2) Is it effective? (3) Is the dose appropriate? (4) Are there safer alternatives? (5) Does it interact with other medications?

Step 3: Prioritize Discontinuation. Start with the most problematic medications (benzodiazepines, anticholinergics, duplicate drug classes). Deprescribe one medication at a time to identify any withdrawal effects or relapse of original condition.

Step 4: Taper or Discontinue. For medications with withdrawal risk (benzodiazepines, antidepressants, lithium), taper gradually. Taper rate varies: benzodiazepines require slow reduction (10% per week); SSRIs can typically be reduced more quickly unless long-term (gradual reduction still preferred).

Step 5: Monitor and Reassess. After discontinuation, monitor for rebound symptoms (anxiety, depression, seizures from benzodiazepine withdrawal) or return of original condition. Document response. Use this experience to inform future prescribing.

4. Behavioral and Psychological Symptoms of Dementia (BPSD): The DICE Approach

Understanding BPSD

Behavioral and psychological symptoms of dementia (agitation, aggression, wandering, sleep disturbance, disinhibition, psychosis) occur in 80%+ of dementia patients at some point. These symptoms are not "part of dementia" to accept passively but rather signals: pain, infection, constipation, environmental stress, unmet needs. Treating the underlying cause often resolves behavior. Pharmacotherapy should be last-resort after behavioral and environmental interventions.

5. Late-Life Depression and Anxiety

Clinical Presentation Differences from Younger Adults

Late-life depression often presents atypically: cognitive complaints ("pseudodementia") may predominate over mood complaints. Somatic symptoms (pain, fatigue, sleep disturbance) are common. Older adults may not describe "sadness" but rather anhedonia, numbness, or "just tired." Medical comorbidities are universal, complicating diagnosis and treatment.

Suicide Risk in Elderly: Adults 65+ account for ~18% of suicide deaths but 16% of the population. Men aged 85+ have the highest suicide rate of any age group (40 per 100,000, vs. 14 per 100,000 overall). Elderly suicides are often more planned and lethal (firearm use higher, more likely to complete vs. attempt). Risk factors include: depression, hopelessness, social isolation, recent loss, medical illness, disability, male gender.

Treatment Selection: SSRIs Preferred

SSRIs are first-line due to favorable side effect profile. Sertraline and citalopram are most commonly used. Start at half the standard dose (sertraline 25–50 mg, citalopram 10 mg) and increase slowly every 2-4 weeks. Expect 4–6 weeks for full response. Hyponatremia risk (SIADH) is higher in elderly; monitor sodium at baseline, week 2, and at symptom development.

SNRIs (venlafaxine) carry hypertension risk; use cautiously. Bupropion has stimulant properties helpful for apathetic depression. TCAs are avoided (anticholinergic effects, falls risk). Psychotherapy (cognitive-behavioral therapy, problem-solving therapy) is highly effective for late-life depression and should be offered adjunctively or as monotherapy for mild-moderate depression.

6. Falls Risk and Psychiatric Medications

Falls are the leading cause of injury death in older adults; one-third of adults 65+ fall annually. Psychiatric medications significantly increase falls risk through multiple mechanisms:

• Benzodiazepines: Sedation, ataxia, impaired balance. Increase falls risk 1.5–2-fold.
• Antipsychotics: Orthostatic hypotension, sedation, parkinsonism. High-risk medications.
• SSRIs: Hyponatremia (causing weakness, confusion), serotonergic effects on gait. Modest increased risk.
• Tricyclics: Anticholinergic effects (urinary retention, confusion), orthostatic hypotension, sedation.
• Lithium: Tremor, ataxia (especially at higher levels or with dehydration), polydipsia leading to frequent toileting.

Fall prevention requires: (1) Minimizing high-risk medications; (2) Regular medication review; (3) Orthostatic vital signs monitoring; (4) Vision/hearing assessment; (5) Physical therapy/balance training; (6) Home safety evaluation; (7) Vitamin D supplementation (if deficient).

7. Delirium Prevention and Management

Delirium (acute, fluctuating altered mental status with inattention) occurs in 20–40% of hospitalized older adults and 80%+ of ICU patients. Psychiatric medications are both risk factors (anticholinergics, opioids, benzodiazepines) and potential causes (medication overdose, withdrawal).

The HELP Program (Hospital Elder Life Program): Evidence-based multicomponent delirium prevention includes: orientation/cognitive stimulation, sleep hygiene (minimize noise/light), early mobilization, vision/hearing correction, volume repletion, and medication review (minimize deliriogenic drugs).

When delirium occurs, management prioritizes finding the cause (infection, hypoxia, medication, dehydration) before resorting to psychotropic medication. If behavioral management fails and medication is necessary, low-dose antipsychotics (haloperidol 0.5–2 mg IV/IM or risperidone 0.5–1 mg) are preferred; benzodiazepines should be avoided unless alcohol/benzodiazepine withdrawal is the cause.