Psychopharmacological Interventions



Psychopharmacological Interventions

WHEN seeing younger adults, mental health practitioners often struggle to convince patients to take even a single medication as part of a treatment plan. Younger adults are not accustomed to taking medications of any kind, let alone those that can influence behavior and cognition, so clinical encounters can become variations on the theme of “take your meds.” In contrast, because many older adults have become accustomed to taking multiple medications for each problem they experience, the clinical theme in work with older adults often becomes “take the right meds” or “take fewer meds.”

To help guide you in striking the right balance between altering, adding, and removing the medications in an older adult’s regimen, we review in this chapter some challenges of prescribing psychotropic medications in older adults, the major classes of these drugs, and considerations involved in determining when, why, and how to discontinue a medication. Our guidance is no replacement for geriatric training, years of experience, or even the knowledge presented in a complete textbook of geriatric psychopharmacology (e.g., Jacobson 2014; Salzman 2005), but we provide some of the lessons we have learned from our experience.

How Aging Affects Pharmacology

As people age, pharmacokinetic and pharmacodynamic changes typically occur in their bodies. As muscle mass decreases and peripheral fat stores increase, lipophilic drugs remain in the body longer. In addition, decreased renal clearance and hepatic blood flow combine to slow the clearance of drugs. The result is that some drug doses build up more quickly in older patients, exerting greater therapeutic and adverse effects at lower doses than expected. Alternatively, some drugs can take longer to be cleared. Therefore, if a practitioner decides to decrease a medication, assessing a patient at a lower dose can take significantly longer with an older adult than with a younger adult. Given these changes in pharmacokinetics that occur with aging, we follow the golden rule for prescribing for older adults: start low, go slow. Table 16–1 summarizes age-related changes affecting pharmacokinetic responses to drugs.

TABLE 16–1. Changes in pharmacokinetics secondary to aging



Effects on prescribing for older adults

Gut absorption

Normal or decreased absorption if delayed gastric emptying or reduced motility


Permeability of blood-brain barrier

Normal or increased permeability if decreased P-glycoprotein pump function in some older adults

Possibly higher drug levels in brain


Increased fat body stores

Longer half-life of lipophilic drugs (most psychotropics)

Higher concentration for water-soluble drugs (e.g., lithium)


Oxidation by CYP enzymes strongly affected by aging; acetylation and methylation unchanged in normal aging

Psychotropics that are CYP substrates may be affected, depending on the type of CYP metabolizer


Decreased renal clearance

Decreased hepatic blood flow

Takes longer to achieve therapeutic blood levels

Higher levels in blood once steady state achieved

Note.   CYP = cytochrome P450.

Source.   Adapted from Jacobson 2014.


Start low. An older adult often needs only 25%–50% of the starting dose and 50%–75% of the effective dose that a younger adult requires.

Go slow. A therapeutic response to new medication often takes longer in older people.

Add one at a time. Before you prescribe a second or adjunctive medication for an older patient, titrate the first medication to the maximum tolerated dose. Avoid highly lipophilic drugs such as diazepam. Because older people have higher fat stores, highly lipophilic drugs may be erratically released.

Medication Noncompliance and Diversion

When a patient’s treatment plan is not proceeding as expected, the practitioner should consider the possibility that the patient may not be taking drugs as instructed; about 20% of prescriptions are never filled, and 50% of medications are not taken as prescribed (Viswanathan et al. 2012). Practitioners should ask patients to bring in their bottles of medications to verify that they are taking the medications correctly. Older patients may not be able to follow through on a regimen for a wide range of reasons, including financial difficulties, cognitive or physical impairment, and intentional dose skipping. Even mild neurocognitive disorder can affect the patient’s ability to comply with straightforward drug regimens, particularly if executive or memory dysfunction is present. Recommended approaches to address each of these problems can be found in Table 16–2.

TABLE 16–2. Approaches to addressing common reasons for medication noncompliance in older adults


Potential solutions

Financial barriers/failure to fill prescriptions

Working with pharmacists to find cheaper alternatives (e.g., 90-day supply vs. 30-day supply, splitting tablets) or cheaper medications in the same class

Working with social services to help patient get insurance

Working with patient to use nonpharmacological interventions such as diet and exercise to improve health status and decrease need for medications

Participation in medication assistance programs, usually sponsored by pharmacy companies

Pharmacy delivery programs

Cognitive impairment

Engaging others to remind patient to take medications

Medication timers

Timed pillboxes, pillbox organizers

Written directions

Coordinating pill taking with meals/bedtime/daily routines

Physical impairment

Non-childproof containers

Blister packs

Talking medication containers

Large-print labels

Easy-to-break tablets

Intentional dose skipping

Education directed toward patient decision making

Practitioner use of open, collaborative communication style in discussing medications with patients

Source.   Adapted from Marek and Antle 2008.

Diversion of medications, particularly of controlled substances, is also a serious issue. Half of individuals age 12 and older who use medications for nonmedical purposes obtained psychotherapeutic drugs and pain relievers for their most recent nonmedical use from a friend or relative, and 80% or more of these users of pain relievers for nonmedical purposes stated that the patients giving away medication received all their drugs from one doctor, which defies the commonly held myth that patients have to shop with multiple practitioners to divert their medications (Substance Abuse and Mental Health Services Administration 2014). Practitioners should be aware of prescription drug misuse as a serious problem among elderly patients. It is best to minimize prescribing as-needed doses of controlled substances such as benzodiazepines, sedative-hypnotics, and stimulants to avoid the stockpiling of medications that may lead to overdoses. If practitioners suspect diversion, they should confirm whether the patients are actually taking their medications by performing an initial urine toxicology screen and confirming the results with gas chromatography/mass spectrometry. Serum drug level testing may be possible for detecting some types of medications. Random urine toxicology screens are generally more informative and minimize manipulation of results.

Failed Medication Trials

Peter is a 77-year-old man who recently moved to be closer to his son and grandchildren. He is visiting your clinic to establish care. During routine screening, he scores 22 on the Patient Health Questionnaire 9-item depression scale (PHQ-9) and, when interviewed, acknowledges that he has been depressed for several years. He is reluctant to initiate treatment, saying, “I already tried three different antidepressants and none worked, so I just live with my depression.” Peter reports that he tried citalopram for 3 days but stopped taking it because of nausea. He then tried fluoxetine for 5 days and quit taking it because “I was feeling more depressed, not less.” Finally, he tried venlafaxine for 2 weeks but stopped when his anxiety worsened.

One of the challenges of prescribing psychotropic medications for older adults is that failed trials are more common among older patients, who have more adverse reactions and higher rates of treatment-resistant depression than the general adult population. We briefly discuss the management of failed medication trials for each category of drugs in the following section, “Classes of Psychotropic Medications Commonly Used With Older Adults.” In general, practitioners should attempt adequate trials of at least two or three lower-price generic psychotropic medications, preferably ones that have different drug mechanisms, before trying a more expensive generic or brand-name psychotropic. Practitioners should also make sure to carefully document the trial of each psychotropic to provide helpful information when referring more complex patients to mental health practitioners. Documentation should include the maximum dose achieved, the length of time the patient was treated at the maximum dose, and the reason for stopping the treatment (e.g., lack of efficacy, undesirable side effect, life-threatening side effect).

Several factors can result in failed medication trials. A patient’s report of a failed medication trial may actually be a report of noncompliance. A failed trial can also be due to the expense of medications. In an effort to save money, many older adults leave prescriptions unfilled, skip doses, or terminate medications prematurely. Adverse effects, both real and perceived, can also result in medication failure. Psychological factors such as the stigma of mental health treatment, preoccupation with adverse effects, or somatic preoccupation can lead a patient to perceive adverse effects that can be resolved only when a practitioner provides education and reassurance. Practitioners often neglect the importance of psychological factors—what is often called the placebo effect—when prescribing a medication. Practitioners need to remember that the prescription of a medication has both implicit and explicit effects on a patient, so they should consider its potential psychological effects. In addition, a patient may erroneously attribute symptoms of mental or physical illness to a psychotropic. For example, a patient may attribute a tremor to a medication when he is actually showing the first signs of Parkinson’s disease, or a patient may report that the first dose of a selective serotonin reuptake inhibitor (SSRI) deepened his depression because he had unrealistic expectations about how the medication works. Prescribing a medication to a patient is only the first step in actually delivering its benefits.

Classes of Psychotropic Medications Commonly Used With Older Adults


Peter has already failed several medication trials for depression, so he has an increased risk of failing another trial. Concerned, you ask Peter about successful medication trials. He tells you that he once took diazepam and describes it as a “magic pill.” He wants any new medication you prescribe to work just as quickly. You discuss the known efficacy and adverse effects of treatments for depression, including initial gastrointestinal effects and the delay between initiating treatment and symptom response. Peter acknowledges anxiety about taking any psychotropic medication because “it will make me look weak.” His budget is also tight, and he is worried about the cost. He agrees to try sertraline because it is the cheapest medication on his prescription formulary. You promise to “start low and go slow” so that Peter can immediately report any side effects that he is experiencing. He eventually agrees to try sertraline at 12.5 mg/day, which he tolerates well, and then agrees to a very slow dose increase to 50 mg/day over the course of 6 weeks. After Peter has taken sertraline 50 mg/day for 2 months, his PHQ-9 score decreases to 13, and he reports subjective improvement of his mental health symptoms. Peter says he does not want to take a higher dose of sertraline because he fears becoming addicted. Despite your multiple attempts to explain that depressive disorder treatments, unlike benzodiazepines, are not habit forming, Peter refuses to consider a higher dose. Therefore, you recommend cognitive-behavioral therapy (CBT) to help achieve full remission of his depressive symptoms. After Peter completes the course of CBT, his PHQ-9 score drops to 3, and he denies any depression during his clinical interview. Following 9 months of persistent work, Peter’s depressive symptoms are now in full remission.

TABLE 16–3. Depressive disorder treatments commonly used in older adults


Recommended starting and target doses

Special concerns



Starting: 10 mg/day

Target: 10–20 mg/day

FDA black box warning recommends not to exceed 20 mg/day in people older than age 60 or who have a history of stroke or cardiac disease


Starting: 5–10 mg/day

Target: 5–20 mg/day

Enantiomer of citalopram

FDA black box warning recommends not to exceed 20 mg/day in people older than age 60 or who have a history of stroke or cardiac disease


Starting: 5–10 mg/day

Target: 5–40 mg/day (60 mg/day for OCD)

Long half-life compared with other SSRIs; needs washout period of 5 weeks before starting TCAs or MAOIs


Starting: 5–10 mg/day

Target: 5–40 mg/day (60 mg/day for OCD)

CR starting: 12.5 mg/day

CR target: 12.5–50 mg/day

Short-half life

Possible anticholinergic side effects


Starting: 12.5–25 mg/day

Target: 25–200 mg/day (higher in OCD)



Starting: 50 mg qod

Target: 50 mg qod or 50 mg/day

Active metabolite of venlafaxine

Discontinue medication gradually to prevent withdrawal symptoms


Starting: 20 mg/day

Target: 20–60 mg/day

Minimize use in patients with end-stage renal disease or hepatic insufficiency

FDA approval for neuropathic pain and fibromyalgia

Discontinue medication gradually to prevent withdrawal symptoms

Lab monitoring: liver function tests at baseline and then as clinically indicated


XR starting: 20 mg/day

XR target: 40–120 mg/day

FDA approval in 2013 for MDD

Limited data in older adults

Discontinue medication gradually to prevent withdrawal symptoms


Starting: 12.5 mg/day

Target: 50–200 mg/day

FDA approval for fibromyalgia, but its enantiomer (levomilnacipran) has FDA approval for depression

Discontinue medication gradually to prevent withdrawal symptoms


IR starting: 25 mg bid

IR target: 150–225 mg/day (bid or tid dosing)

XR starting: 37.5 mg/day

XR target: 150–225 mg/day (once-daily dosing)

XR form preferable to IR to prevent withdrawal symptoms

Missing doses (particularly IR) can cause unpleasant withdrawal symptoms

Discontinue medication gradually to prevent withdrawal symptoms



Starting: 25 mg/day

Target: 25–150 mg/day

Therapeutic serum level > 115 ng/mL; potential toxicity at > 300 ng/mL


Starting: 10 mg/day

Target: 10–100 mg/day

Therapeutic serum level 50–150 ng/mL


Selegiline (transdermal)

Starting: 6 mg/day

Target: 6–12 mg/day

No dietary restrictions at 6 mg/day (or 2 weeks after reducing dosage from 12 to 6 mg/day)

Hold patch at least 10 days prior to elective surgery with general anesthesia

Other classes

Bupropion (IR, SR, XL formulations)

IR starting: 37.5–75 mg qam

IR target: 75–225 mg/day

SR starting: 100 mg qam

SR target: 100–300 mg/day

XL starting: 150 mg qam

XL target: 150–300 mg/day

Norepinephrine and dopamine reuptake inhibitor

Low risk of seizure (< 0.5%) for dosages ≤ 450 mg/day


Starting: 7.5 mg qhs

Target: 7.5–45 mg/day

α2-Adrenergic inhibitor

Histaminergic properties at low doses (sedation, increased appetite)

St. John’s wort

Starting 300 mg tid

Target: 300 mg tid

Do not take concurrently with serotonergic medications (e.g., SSRIs, SNRIs, MAOIs)



Starting: 25 mg qhs

Target: 25–50 mg qhs


Starting: 75 mg qhs

Target: 75–375 mg qhs

5-HT2A/2C and α1-adrenergic antagonist

Mainly used as off-label treatment for insomnia because target doses used for depression cause sedation


Starting: 10 mg/day

Target: 20–40 mg/day

Selective 5-HT reuptake inhibitor and 5-HT1A partial agonist

FDA approval in 2011 for MDD

Limited data in older adults


Starting: 10 mg/day

Target: 20–40 mg/day

Multiple effects on 5-HT receptors (partial 5-HT1B receptor agonism, 5-HT7 antagonism, 5-HT3 antagonism); inhibition of the 5-HT transporter

Note.   5-HT = serotonin; bid = twice daily; CR = controlled release; FDA = U.S. Food and Drug Administration; IR = immediate release; MAOI = monoamine oxidase inhibitor; MDD = major depressive disorder; OCD = obsessive-compulsive disorder; qam = every morning; qhs = every night; qod = every other day; SNRI = serotonin-norepinephrine reuptake inhibitor; SR = sustained release; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; tid = three times daily; XL = extended release; XR = extended release.

Source.   Asnis and Henderson 2015; Croft et al. 2014; Davidson 1989; Gury and Cousin 1999; Jacobson 2014; Laughren et al. 2011; U.S. Food and Drug Administration 2011.

The medications that are commonly used to treat depressive disorders are listed in Table 16–3. The classes of first-line treatments for depression include SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine and dopamine reuptake inhibitors, and α2-adrenergic and serotonergic antagonists. Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are second-line treatments because of their adverse-effect profiles (including anticholinergic side effects for TCAs and dietary restrictions for MAOIs) and the higher likelihood of lethality if patients overdose on them. In general, the first-line treatments have similar efficacy (e.g., Fournier et al. 2010). The decision to use a first-line treatment is based on several factors, including tolerability by the patient; the potential for dual benefits (e.g., duloxetine to treat both major depressive disorder and diabetic neuropathy), which helps minimize polypharmacy; better adverse-effect profile; and cost.

The rule to start low, go slow is especially important when treating depression. Many older adults will discontinue SSRIs or SNRIs because of adverse gastrointestinal effects, even though the effects can be minimized by taking the medication with food and typically resolve during the first week or two of treatment. Some older adults experience paradoxical anxiety if an SSRI or SNRI is started at too high a dose or titrated too quickly.

Because only about 50% of older adults respond adequately to an optimal trial of a first-line treatment (Lenze et al. 2008), practitioners often need to consider a course of psychotherapy, the initiation of electroconvulsive therapy, or the addition of a second or adjunctive psychotropic medication. The National Institute of Mental Health–funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, which included patients from both mental health and primary care settings, studied how those who failed to respond to a previous treatment for depression responded to a subsequent treatment. Although the STAR*D study examined the general adult population, many of its findings are useful for older adults. Some of the major findings were that 1) full response can take as long as 10–12 weeks; 2) with every additional treatment required to treat depression, the likelihood of success decreased; 3) patients who had full remission did better than those who had partial remission of their depressive symptoms; and 4) patients who needed more than one treatment attempt were more likely to have severe depressive symptoms and comorbid psychiatric and medical problems (National Institute of Mental Health 2006). Given these results, practitioners in primary care should discuss with their patients how long it can take to respond to depressive disorder treatments and caution that more than one trial may be needed to treat depression effectively.


Treatments studied for bipolar disorder can be used in older adults to treat various mental health symptoms, including but not limited to manic symptoms due to primary psychiatry disorder and secondary causes, depressive symptoms in bipolar disorder, and mood dysregulation. Most agents, except lithium, were first studied and approved for the treatment of seizure disorders. Because these medications have multiple potential indications, it is important for a practitioner to document the specific indication for each medication—for example, epilepsy, neuropathic pain, or mood instability—so that other practitioners will know why each medication has been prescribed before electing to continue or discontinue it. In general, these medications should be carefully titrated up and down, because abrupt discontinuation can result in withdrawal seizures.

As a general rule, lithium and valproic acid are first-line treatments for bipolar disorders. Among older adults with bipolar disorder, lithium is efficacious but is difficult to take because of its narrow therapeutic index, the number of drug-drug interactions (especially with thiazide diuretics and nonsteroidal anti-inflammatory drugs), and its adverse effects (renal impairment, tremor, and cognitive dysfunction). Because of these difficulties, many geriatric mental health practitioners prefer to use valproic acid when treating patients with bipolar disorders. If valproic acid is not efficacious or cannot be tolerated, second-line treatments include levetiracetam, lamotrigine, and carbamazepine, all of which present a number of challenges. They require careful titration upward, and therefore, therapeutic effects can take longer. In particular, lamotrigine also has a number of drug-drug interactions, which affect its titration schedule. The titration schedule must be carefully followed because of the known risk of Stevens-Johnson syndrome (Table 16–4). Carbamazepine causes autoinduction of cytochrome P450 (CYP) 3A4, inducing CYP3A4 but also a substrate of CYP3A4, which can result in reduced efficacy 2–3 weeks after a stable dose is achieved.

TABLE 16–4. Bipolar disorder treatments commonly used in older adults


Recommended starting and target doses

Therapeutic serum level

Special concerns


Starting: 100 mg bid

Target: 200–800 mg/day (divided bid)

4–12 µg/mL

Because of anticholinergic effects, should be reserved as a last-line treatment

Autoinduction may lower levels after 2–3 weeks of treatment, so dose may need to be increased

Slow titration upward to decrease likelihood of Stevens-Johnson syndrome

Start at 100–200 mg/day and then increase at weekly intervals on the basis of observed symptoms

Can also be used for seizure management

Lab monitoring: serum level at baseline and then 2–4 weeks later to monitor for autoinduction; CBC, basic metabolic panel including blood urea nitrogen and creatinine, LFTs at baseline and then every 3–12 months as clinically indicated

Divalproex (valproate, valproic acid)

Starting: 125–250 mg qd to bid

Target: 250–1,500 mg/day (divided bid, except XR is dosed once daily)

65–90 µg/mL

Adjustment phase: VPA levels every 1–2 weeks

CBCs, LFTs every 4 weeks for first 2 months

Maintenance phase: depakote every 3 months; CBCs, LFTs every 6 months

Can also be used for seizure management


Starting: 25 mg qd or qod (see special concerns)

Target: 100–200 mg/day

Therapeutic serum level for psychiatric disorder unknown

Increase by 25–50 mg/day every 2 weeks

Slow titration upward to decrease likelihood of Stevens-Johnson syndrome (see Table 16–5)

Stevens-Johnson syndrome usually occurs within 2–8 week of initiation; lamotrigine should be stopped at the first sign of any rash, even if it appears benign

Therapeutic dosage sensitive to drug-drug interactions (see Table 16–5)

Can also be used for seizure management


Starting: 250 mg bid

Target: 250–1,500 mg/day (divided bid or tid)

Therapeutic serum level for psychiatric disorder unknown

Some evidence for anti–manic behavior in dementia

Increase by 250–500 mg/day every week

Can also be used for seizure management


Starting: 75–150 mg qhs

Target: 150–1,800 mg/day (usually 300–900 mg/day)

0.4–1.0 mEq/L

Therapeutic benefit and toxicity may occur at lower serum levels in older adults because of changes in blood-brain barrier

Educate patients about interactions with drugs, especially common over-the-counter drugs, and importance of maintaining consistent salt intake and hydration

Consider more frequent lab monitoring in patients with large fluid shifts or renal insufficiency (lithium is renally cleared)

Consider MedicAlert bracelet for patients who take lithium

Lab monitoring: first lithium level after steady state achieved (usually 5 days), then every 3–12 months as clinically indicated; ECG, blood urea nitrogen, creatinine, and thyroid-stimulating hormone at baseline and then every 3–12 months as clinically indicated

Note.   bid = twice daily; CBC = complete blood count; ECG = electrocardiogram; LFT = liver function test; qd = every day; qhs = at bedtime; qod = every other day; tid = three times daily; VPA = valproate; XR = extended release.

Source.   Cullison et al. 2014; GlaxoSmithKline 2015; Jacobson 2014. Novartis 2015.

TABLE 16–5. Adjustments for starting dose and titration schedule for patients taking drugs that interact with lamotrigine

Patients not taking carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid

Patients taking valproic acid

Patients taking carbamazepine, phenytoin, phenobarbital, or primidone but not valproic acid

Effect on lamotrigine


Increases lamotrigine levels

Decreases lamotrigine levels

Adjustments for starting dose and titration schedule of lamotrigine

Follow standard titration schedule for lamotrigine

Starting dose: 25 mg/day

Ending dose: 200 mg/day at week 7

Decrease starting dose of lamotrigine by 50% (25 mg every other day) and slow the titration schedule by 50% (100 mg/day at week 7)

Increase starting dose of lamotrigine by 50% (50 mg/day) and speed up the titration schedule by 50% (400 mg/day at week 7)

Source.   Adapted from GlaxoSmithKline 2015.

Although a non–mental health practitioner may feel comfortable beginning an initial treatment for bipolar disorder, the treatment of an older adult with a manic, hypomanic, or bipolar depression is often complicated. For example, practitioners should be aware of the drugs that may interact with lamotrigine (Table 16–5) and should carefully review the lamotrigine drug insert for how certain drugs may affect the lamotrigine initiation and titration schedule (GlaxoSmithKline 2015). In addition, many patients who have bipolar disorder as a primary psychiatric disorder are often noncompliant with treatment, so more intensive mental health services may be needed to ensure that they remain stable.


Treatments for schizophrenia and other psychotic disorders are often called “antipsychotics,” but leading psychiatrists prefer to describe them on the basis of their mechanism of action (Zohar et al. 2014). Naming these medications by their mechanism of action helps practitioners understand why they are efficacious both for the treatment of psychotic disorders and as adjunctive medications for depressive, anxiety, and bipolar disorders. In Table 16–6, we review the commonly prescribed medications to treat psychotic disorders, including special concerns for their administration to older adults. Most treatments for psychotic disorders antagonize the dopamine type 2 (D2) receptor, but many newer medications antagonize the D2 receptor and modulate the serotonin (5-HT) receptors by acting as partial agonists at the 5-HT1A receptor and antagonists at the 5-HT2A receptor. These additional actions may ameliorate some of the undesirable side effects seen with medications that primarily antagonize the D2 receptor, such as tardive dyskinesia and extrapyramidal symptoms (Meltzer 2013).

TABLE 16–6. Psychotic disorder treatments commonly used in older adults


Recommended starting and target doses

Special concerns


Tablet or solution starting: 2–5 mg/day

Tablet or solution target: 2–20 mg/day

LAI starting: 400 mg IM every 4 weeks

LAI target: 300–400 mg IM every 4 weeks

LAI not well studied in elderly and should not be used in those with dementia

Initial dose for LAI should be 400 mg, but dose can be decreased to 300 mg if adverse reaction occurs


Starting: 5 mg bid

Target: 5 mg/day to 10 mg bid

Newer medication with only one small study of asenapine in older adults with bipolar disorder (Scheidemantel et al. 2015)


Starting: 6.25–12.5 mg/day

Target: 7.25–400 mg/day

Increase 25–50 mg/day for first 2 weeks, and then no more than 100 mg 1–2 times per week

Weekly CBCs to monitor for leukopenia unless ANC < 1,500/µL (see Clozapine REMS Web site for more details [])

Usually reserved for patients with psychotic disorders refractory to other treatments

Side effects include agranulocytosis, seizures, myocarditis, orthostatic hypotension


Oral starting: 1–2.5 mg/day

Target: 0.25–4 mg/day (divided)

Depot form available


Oral starting: 0.25–0.5 mg qd to tid; target: 0.25–4 mg qd

IV formulation reserved for settings with telemetry

Decanoate starting: 25 mg/month Decanoate target: 25–100 mg/month

Depot form available


Starting: 1 mg bid

Target: 6–12 mg bid

Titration packet available

Not well studied in elderly

Orthostatic hypotension


Starting: 40 mg/day

Target: 40–80 mg/day

Two studies in older adults (Forester et al. 2015; Sajatovic et al. 2016)


Oral starting: 2.5 mg/day

Oral target: 2.5–15 mg/day

LAI starting: 150 mg im every 4 weeks

LAI target: 150–300 mg im every 4 weeks

LAI not well studied in elderly and should be avoided because of risk of postinjection delirium (a side effect unique to olanzapine LAI) (Rauch and Fleischhacker 2013)


XR starting: 3 mg/day

XR target: 3–12 mg/day

LAI starting: 156 mg IM every 4 weeks

LAI target: 39–234 mg every 4 weeks

Therapeutic serum level: 3.5–50 ng/mL

One small study in older adults (Tzimos et al. 2008)


Starting: 2–4 mg qd to bid

Target: 2–32 mg/day

Poor CYP D26 metabolizers

Patients taking CYP D26 inhibitors (e.g., TCAs, SSRIs) may have higher plasma levels (Schering Corporation 2002)


IR tablets starting: 12.5–50 mg qhs

IR tablets target: 12.5–400 mg (divided bid to tid)

XR tablets starting: 50 mg qhs

XR tablets target: 50–400 mg qhs

Orthostatic hypotension

Plasma levels may increase when quetiapine is administered with CYP 3A inhibitors (e.g., ketoconazole, erythromycin) (AstraZeneca 2003)


Oral starting: 0.25–0.5 mg qhs

Oral target: 0.25–3 mg qd or bid

LAI starting: 25 mg IM every 2 weeks

LAI target: 12.5–50 mg IM every 2 weeks

Limited studies support efficacy of LAI in older adults with schizophrenia (Catalán and Penadés 2011)


Oral starting: 20 mg bid

Oral target: 20–80 mg bid

Rare but serious skin reaction known as drug reaction with eosinophilia and systemic symptoms (DRESS) (U.S. Food and Drug Administration 2014a)

Note.   ANC = absolute neutrophil count; bid = twice daily; CBC = complete blood count; CYP = cytochrome P450; im = intramuscular; IR = immediate release; IV = intravenous; LAI = long-acting injectable; qd = every day; qhs = every night; REMS = Risk Evaluation and Mitigation Strategy; tid = three times daily; XR = extended release; SSRIs = selective serotonin reuptake inhibitors; TCAs = tricyclic antidepressants.

Consider QTc monitoring for patients on both typical and atypical antipsychotics if they have a number of risk factors for QTc prolongation (e.g., history of cardiac arrhythmias).

Source.   Clozapine REMS Program 2014; Jacobson 2014.

When practitioners prescribe a medication that antagonizes the D2 receptor, they should understand which mental health symptoms or disorders they are targeting and how long they anticipate prescribing the medication. This is important not only for communication among all practitioners involved in a patient’s care but also to determine whether a psychotic disorder treatment can be tapered or discontinued. It is crucial to be vigilant about psychotic disorder treatments, which may have significant adverse effects in all adults but especially in older adults.

Most practitioners are aware that medications that antagonize the D2 receptors are associated with a higher risk of tardive dyskinesia and extrapyramidal symptoms. Medications that antagonize the D2 receptor and modulate the 5-HT receptors are associated with metabolic syndrome and require special monitoring. Measurements that should be obtained at baseline, 12 weeks, and annually are body mass index (BMI), waist circumference, blood pressure, fasting glucose/hemoglobin A1c, and lipids. BMI should also be measured at 4 weeks, 8 weeks, and then every 3 months (American Diabetes Association et al. 2004).

Fewer practitioners are aware that all medications that antagonize the D2 receptors increase risk of stroke, QTc prolongation that predisposes to the potentially life-threatening torsades de pointes, and sudden death (Ray et al. 2009) or that these medications are associated with cognitive decline when prescribed to patients with dementia (Vigen et al. 2011). Practitioners should discuss and document these serious adverse effects with patients. Given the overall concerns regarding adverse effects and alterations in metabolism in older adults, long-acting injectable versions should be reserved mainly for patients with chronic psychotic disorders living in the community who have demonstrated noncompliance; they should not be used in patients who have dementia with behavioral disturbances.

Finally, clozapine deserves special attention. Clozapine is an underutilized treatment for persons with psychotic disorders (Stroup et al. 2016), but prescribing it is complicated because of the risk of serious adverse effects, especially agranulocytosis, and the associated requirement for gradual titration and discontinuation. In the United States, all practitioners who prescribe clozapine and all pharmacists who dispense it are required to register in the Clozapine REMS Program. The monitoring guidelines for patients before they start and while they are taking clozapine, as well as the indications for discontinuation versus more intensive monitoring when neutropenia develops, have now been standardized by the Clozapine REMS Program. Information is available on the Clozapine REMS Web site (


Older adults frequently present for treatment of anxiety and insomnia. In the past, practitioners typically prescribed benzodiazepines to older adults experiencing anxiety and insomnia, but accumulating evidence suggests that these drugs are associated with a higher risk of falls and dementia (Woolcott et al. 2009). Today, practitioners should work to minimize the use of benzodiazepines in older adults and to discontinue their use among older adults who have become both physiologically and psychologically dependent on these medications. We discuss recommendations for tapering benzodiazepines in the next section, “Medication Discontinuation in Older Adults.”

Buspirone and the psychotherapies described in Chapter 15, “Psychotherapeutic Interventions,” are safer alternatives to benzodiazepines in older adults. Benzodiazepine derivatives are also commonly used as hypnotics in older adults. Z-drugs (e.g., zolpidem, zaleplon, zopiclone) are similar to benzodiazepines and have the same long-term concerns about dependence. Medications that act on other receptors, such as ramelteon, a melatonin receptor agonist, and suvorexant, an orexin receptor antagonist, need further studies in older adults. Ramelteon appears to have the potential to prevent delirium (Hatta et al. 2014). Doxepin at low doses (3–6 mg) is also approved for insomnia and can be useful for older adults (Rojas-Fernandez and Chen 2014). Practitioners should work up patients for sleep-wake disorders, particularly obstructive sleep apnea; review sleep hygiene guidelines; and refer patients for CBT for insomnia (CBT-I). In Table 16–7, we review commonly used treatments and discuss special concerns for their use among older adults.

TABLE 16–7. Anxiety and sleep-wake disorder treatments commonly used in older adultsa


Recommended starting and target doses

Special concerns


Starting: 5 mg bid

Target: 5 mg bid to 20 mg tid

Doxepin (low-dose)a

Starting: 3 mg qhs

Target: 3–6 mg qhs

Less likely to have anticholinergic effects at low doses


Starting: Difficulty with sleep initiation 1 mg; difficulty with sleep maintenance 2 mg

Target:1–2 mg qhs


Starting: Anxiety: 100 mg every 12 hours; insomnia 100 mg qhs

Target: Anxiolytic effect 200–1,800 mg/day; insomnia 100–300 mg qhs

Has FDA approval only for neuralgia and epilepsy; use for anxiety or insomnia is off-label


Starting: Anxiety 0.25–0.5 mg qd to bid; insomnia 0.25–0.5 mg qhs

Target: 0.25–2 mg/day


Starting: 0.5–6 mg/qhs (within 30–120 minutes of bedtime)

Target: 1–6 mg/qhs

FDA considers melatonin to be a dietary supplement, not a drug


Starting: 8 mg (within 30 minutes of bedtime)

Target: 8 mg (within 30 minutes of bedtime)

Mechanism: melatonin receptor agonist

Limited evidence for preventive use in delirium (Hatta et al. 2014)


Starting: 10 mg qhs

Target: 10–40 mg qhs

Mechanism: orexin receptor antagonist

Limited knowledge about effects in elderly

Unlike benzodiazepines and Z-drugs, suvorexant has no known effects in mild to moderate obstructive sleep apnea (Sun et al. 2016)


Starting: 5 mg qhs

Target: 5–10 mg immediately before bedtime


Starting: IR 5 mg qhs

CR: 6.25 mg immediately before bedtime

Target: IR 5–10 mg qhs

CR: 6.25–12.5 mg qhs

Lower doses for women because they are at higher risk for neuropsychiatric effects (hallucinations/sensory distortion, amnesia, sleepwalking, and nocturnal eating)

Zolpidem is the psychotropic drug most commonly implicated in emergency department visits for adverse medication events in older adults (Hampton et al. 2014)

Assess for motor impairment, particularly in patients who are driving

FDA advises against next-day driving in patients taking Ambien CR (U.S. Food and Drug Administration 2016)

Note.   bid = twice daily; CR = controlled release; FDA = U.S. Food and Drug Administration; IR = immediate release; qd = every day; qhs = every night; tid = three times daily.

aBenzodiazepines and Z-drugs should be used with caution because of the risks of increased falls and dementia. These should ideally be prescribed on a short-term basis except in rare circumstances such as end-of-life or palliative care cases.

Source.   Bennett et al. 2014; Jacobson 2014; U.S. Food and Drug Administration 2014b, 2016.

Medication Discontinuation in Older Adults: Stopping the Epidemic of Polypharmacy

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Sep 1, 2019 | Posted by in PSYCHOLOGY | Comments Off on Psychopharmacological Interventions
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