Treating Behavioral and Psychological Symptoms of

Dementia (BPSD)

Kuang-Yang Hsieh, M.D. ph.D.Kuang-Yang Hsieh, M.D. ph.D.

Department of PsychiatryDepartment of Psychiatry

Chimei Medical CenterChimei Medical Center

(DLB)

(PD)

(FTD)

60 %

20 %

Role of neurologist and psychiatrist Role of neurologist and psychiatrist in the course of dementiain the course of dementia

Neurologist: Identification and correction of risk factors; Early diagnosis and intervention

Mild Cognitive Impairment Dementia

Psychiatrist: Early diagnosis and intervention;Treating BPSD

Treatment of BPSDTreatment of BPSD

Use non-pharmacological treatment first.Use non-pharmacological treatment first. Use of psychiatric medication is not routinely Use of psychiatric medication is not routinely

recommended unless the problem is severe . recommended unless the problem is severe .

In patients with BPSD, the mortality rate was In patients with BPSD, the mortality rate was 1.6–1.7-fold higher in the antipsychotics-1.6–1.7-fold higher in the antipsychotics-treated group than in the placebo-treated treated group than in the placebo-treated group.group.

Points for attention about Points for attention about pharmacotherapy of BPSDpharmacotherapy of BPSD

Sedative and anticholinergic effects of medications may impede cognitive functions.cognitive functions.

Patients with PD or DLB are especially sensitive to extrapyramidal symptomsextrapyramidal symptoms.

Start low and go slow.Start low and go slow. Be careful of the motor, cognitive, metabolic and Be careful of the motor, cognitive, metabolic and

vascular effects of medications.vascular effects of medications. Beware of the Beware of the risk of falls.risk of falls.

Assess risk and benefit.Assess risk and benefit.

Cholinesterase inhibitors Cholinesterase inhibitors and memantine are helpful and memantine are helpful for BPSD.for BPSD.

Antipsychotics are effective for Antipsychotics are effective for delusion, hallucination, agitation and delusion, hallucination, agitation and aggression.aggression.

Second-generation antipsychotics are Second-generation antipsychotics are recommended. recommended. (Risperdal, Zyprexa, (Risperdal, Zyprexa, Clozaril, SoLian, Abilify)Clozaril, SoLian, Abilify)

Beware of EPS, orthostatic hypotension Beware of EPS, orthostatic hypotension and metabolic adverse effects.and metabolic adverse effects.

Anticonvulsants are not helpful for Anticonvulsants are not helpful for BPSD.BPSD.

If there is significant poststroke or If there is significant poststroke or posttraumatic epilepsy, choose an posttraumatic epilepsy, choose an anticonvulsant with less cognitive adverse anticonvulsant with less cognitive adverse effects.effects.

Depakine (valproate) and Lamictal Depakine (valproate) and Lamictal (lamotrigine) are recommended.(lamotrigine) are recommended.

Antidepressants are effective for Antidepressants are effective for depression and anxietydepression and anxiety

Tricyclic antidepressants (TCAs)Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors (SSRIs) Selective serotonin reuptake inhibitors (SSRIs) Serotonin and norepinephrine reuptake inhibitSerotonin and norepinephrine reuptake inhibit

ors (SNRIs) ors (SNRIs) Norepinephrine and specific serotonin antideprNorepinephrine and specific serotonin antidepr

essant (NaSSA) essant (NaSSA) Norepinephrine and dopamine reuptake inhibitNorepinephrine and dopamine reuptake inhibit

or (NDRI)or (NDRI) Other serotonin modulatorsOther serotonin modulators

Tricyclic antidepressants (TCAs)Tricyclic antidepressants (TCAs)

Example: Sinequan (doxepin), Tofranil Example: Sinequan (doxepin), Tofranil (imipramine), Deanxit (melitracen)(imipramine), Deanxit (melitracen)

Inhibiting the reuptake of Inhibiting the reuptake of norepinephrine and serotonin; blocking norepinephrine and serotonin; blocking histamine (H1), alpha1-adrenergic and histamine (H1), alpha1-adrenergic and muscarinic receptors.muscarinic receptors.

Effective for neurogenic pain at low Effective for neurogenic pain at low doses.doses.

Tricyclic antidepressants (TCAs)Tricyclic antidepressants (TCAs)

Prominent side effects due to receptor Prominent side effects due to receptor blocking (sedation, hypotension, blocking (sedation, hypotension, blurred vision, constipation, urinary blurred vision, constipation, urinary retention, dry mouth, exacerbation of retention, dry mouth, exacerbation of glaucoma, cognitive impairment).glaucoma, cognitive impairment).

Overdose may be lethal, with Overdose may be lethal, with cardiovascular and CNS toxicity.cardiovascular and CNS toxicity.

Not recommended for BPSD.Not recommended for BPSD.

Selective serotonin reuptake Selective serotonin reuptake inhibitors (SSRIs)inhibitors (SSRIs)

Example: Prozac (fluoxetine), Zoloft (sertraline)Example: Prozac (fluoxetine), Zoloft (sertraline) Being more safe, causing less side effects than TCAs. Being more safe, causing less side effects than TCAs. Inhibiting cytochrome P450 enzymes, thus Inhibiting cytochrome P450 enzymes, thus

increasing the concentration of co-administered increasing the concentration of co-administered medication.medication.

Side effects: insomnia, sexual dysfunction, Side effects: insomnia, sexual dysfunction, nausea/vomiting. (through 5-HT1, 5-HT2, 5-HT3 nausea/vomiting. (through 5-HT1, 5-HT2, 5-HT3 receptor signaling respectively)receptor signaling respectively)

Effective for disinhibition, impulsivity and repetitive Effective for disinhibition, impulsivity and repetitive behavior in FTD.behavior in FTD.

Serotonin and norepinephrine Serotonin and norepinephrine reuptake inhibitors (SNRIs)reuptake inhibitors (SNRIs)

Example: Efexor (venlafaxine), Example: Efexor (venlafaxine), Cymbalta (duloxetine)Cymbalta (duloxetine)

More effective for pain and anxiety More effective for pain and anxiety symptoms than SSRIs.symptoms than SSRIs.

Side effects: insomnia, sexual Side effects: insomnia, sexual dysfunction, nausea/vomiting.dysfunction, nausea/vomiting.

Norepinephrine and specific Norepinephrine and specific serotonin antidepressant serotonin antidepressant (NaSSA)(NaSSA) Example: Remeron (mirtazapine)Example: Remeron (mirtazapine) Indirectly increasing synaptic norepinephrine and Indirectly increasing synaptic norepinephrine and

serotonin through blockade of central presynaptic serotonin through blockade of central presynaptic alpha2-adrenergic receptors.alpha2-adrenergic receptors.

Blocking histamine (H1), 5-HT2 and 5-HT3 receptors.Blocking histamine (H1), 5-HT2 and 5-HT3 receptors. Causing less insomnia, sexual dysfunction, Causing less insomnia, sexual dysfunction,

nausea/vomiting than SSRIs.nausea/vomiting than SSRIs. Effective for pain, insomnia and anorexia/cachexia.Effective for pain, insomnia and anorexia/cachexia. Side effects: sedation, increased appetite, weight gain.Side effects: sedation, increased appetite, weight gain.

Norepinephrine and dopamine Norepinephrine and dopamine reuptake inhibitor (NDRI)reuptake inhibitor (NDRI)

Example: Wellbutrin (bupropion)Example: Wellbutrin (bupropion) Effective for fatigue, loss of energy.Effective for fatigue, loss of energy. Causing less sexual dysfunction than SSRIs; Causing less sexual dysfunction than SSRIs;

may improve sexual dysfunction associated may improve sexual dysfunction associated with chemotherapy and hormonal therapy.with chemotherapy and hormonal therapy.

Additional benefit for smoking cessationAdditional benefit for smoking cessation .. Side effects: insomnia, tachycardia, seizure.Side effects: insomnia, tachycardia, seizure.

Other serotonin modulatorsOther serotonin modulators

Example: Mesyrel (trazodone)Example: Mesyrel (trazodone) Inhibiting serotonin reuptake; blocking Inhibiting serotonin reuptake; blocking

histamine (H1) and alpha1-adrenergic histamine (H1) and alpha1-adrenergic receptors.receptors.

Usually used as a hypnoticUsually used as a hypnotic (10-100 mg/d) (10-100 mg/d) rather than an antidepressant (200-400 mg/d).rather than an antidepressant (200-400 mg/d).

Decreasing number of awakenings, increasing Decreasing number of awakenings, increasing total sleep time and percentage of deep sleep total sleep time and percentage of deep sleep (stages 3+4). (stages 3+4).

Side effects: sedation, hypotension, dizziness.Side effects: sedation, hypotension, dizziness.

Pharmacotherapy for insomniaPharmacotherapy for insomnia

Mesyrel (trazodone) is the drug of choice.Mesyrel (trazodone) is the drug of choice. Be careful of sedative and muscle-Be careful of sedative and muscle-

relaxing effects of benzodiazepines. Avoid relaxing effects of benzodiazepines. Avoid using them in patients with BPSD.using them in patients with BPSD.

ConclusionConclusion

BPSD should be appropriately treated.BPSD should be appropriately treated. Consider Non-pharmacological treatment Consider Non-pharmacological treatment

first. Reserve pharmacotherapy for the first. Reserve pharmacotherapy for the second line. second line.

Medication for each patient should be Medication for each patient should be individually taylored. Risk and benefit individually taylored. Risk and benefit should be carefully assessed.should be carefully assessed.

Consult the psychiatrist when the problem Consult the psychiatrist when the problem becomes obvious and out of control. becomes obvious and out of control.

Thank you for attentionThank you for attention