Treating Behavioral and Psychological Symptoms of Dementia (BPSD) Kuang-Yang Hsieh, M.D. ph.D. Department of Psychiatry Chimei Medical Center

(DLB) (PD) (FTD) 60 % 20 %

Role of neurologist and psychiatrist in the course of dementia Neurologist: Identification and correction of risk factors; Early diagnosis and intervention Mild Cognitive ImpairmentDementia Psychiatrist: Early diagnosis and intervention; Treating BPSD

Treatment of BPSD Use non-pharmacological treatment first. Use non-pharmacological treatment first. Use of psychiatric medication is not routinely recommended unless the problem is severe. Use of psychiatric medication is not routinely recommended unless the problem is severe. In patients with BPSD, the mortality rate was 1.6–1.7-fold higher in the antipsychotics- treated group than in the placebo-treated group. In patients with BPSD, the mortality rate was 1.6–1.7-fold higher in the antipsychotics- treated group than in the placebo-treated group.

Points for attention about pharmacotherapy of BPSD cognitive functions. Sedative and anticholinergic effects of medications may impede cognitive functions. extrapyramidal symptoms Patients with PD or DLB are especially sensitive to extrapyramidal symptoms. Start low and go slow. Start low and go slow. Be careful of the motor, cognitive, metabolic and vascular effects of medications. Beware of the risk of falls. Be careful of the motor, cognitive, metabolic and vascular effects of medications. Beware of the risk of falls. Assess risk and benefit. Assess risk and benefit.

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

Antipsychotics are effective for delusion, hallucination, agitation and aggression. Antipsychotics are effective for delusion, hallucination, agitation and aggression. Second-generation antipsychotics are recommended. (Risperdal, Zyprexa, Clozaril, SoLian, Abilify) Second-generation antipsychotics are recommended. (Risperdal, Zyprexa, Clozaril, SoLian, Abilify) Beware of EPS, orthostatic hypotension and metabolic adverse effects. Beware of EPS, orthostatic hypotension and metabolic adverse effects.

Anticonvulsants are not helpful for BPSD. Anticonvulsants are not helpful for BPSD. If there is significant poststroke or posttraumatic epilepsy, choose an anticonvulsant with less cognitive adverse effects. If there is significant poststroke or posttraumatic epilepsy, choose an anticonvulsant with less cognitive adverse effects. Depakine (valproate) and Lamictal (lamotrigine) are recommended. Depakine (valproate) and Lamictal (lamotrigine) are recommended.

Antidepressants are effective for depression and anxiety Tricyclic antidepressants (TCAs) Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors (SSRIs) Selective serotonin reuptake inhibitors (SSRIs) Serotonin and norepinephrine reuptake inhibitors (SNRIs) Serotonin and norepinephrine reuptake inhibitors (SNRIs) Norepinephrine and specific serotonin antidepressant (NaSSA) Norepinephrine and specific serotonin antidepressant (NaSSA) Norepinephrine and dopamine reuptake inhibitor (NDRI) Norepinephrine and dopamine reuptake inhibitor (NDRI) Other serotonin modulators Other serotonin modulators

Tricyclic antidepressants (TCAs) Example: Sinequan (doxepin), Tofranil (imipramine), Deanxit (melitracen) Example: Sinequan (doxepin), Tofranil (imipramine), Deanxit (melitracen) Inhibiting the reuptake of norepinephrine and serotonin; blocking histamine (H1), alpha1-adrenergic and muscarinic receptors. Inhibiting the reuptake of norepinephrine and serotonin; blocking histamine (H1), alpha1-adrenergic and muscarinic receptors. Effective for neurogenic pain at low doses. Effective for neurogenic pain at low doses.

Tricyclic antidepressants (TCAs) Prominent side effects due to receptor blocking (sedation, hypotension, blurred vision, constipation, urinary retention, dry mouth, exacerbation of glaucoma, cognitive impairment). Prominent side effects due to receptor blocking (sedation, hypotension, blurred vision, constipation, urinary retention, dry mouth, exacerbation of glaucoma, cognitive impairment). Overdose may be lethal, with cardiovascular and CNS toxicity. Overdose may be lethal, with cardiovascular and CNS toxicity. Not recommended for BPSD. Not recommended for BPSD.

Selective serotonin reuptake 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 increasing the concentration of co-administered medication. Inhibiting cytochrome P450 enzymes, thus increasing the concentration of co-administered medication. Side effects: insomnia, sexual dysfunction, nausea/vomiting. (through 5-HT1, 5-HT2, 5-HT3 receptor signaling respectively) Side effects: insomnia, sexual dysfunction, nausea/vomiting. (through 5-HT1, 5-HT2, 5-HT3 receptor signaling respectively) Effective for disinhibition, impulsivity and repetitive behavior in FTD. Effective for disinhibition, impulsivity and repetitive behavior in FTD.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) Example: Efexor (venlafaxine), Cymbalta (duloxetine) Example: Efexor (venlafaxine), Cymbalta (duloxetine) More effective for pain and anxiety symptoms than SSRIs. More effective for pain and anxiety symptoms than SSRIs. Side effects: insomnia, sexual dysfunction, nausea/vomiting. Side effects: insomnia, sexual dysfunction, nausea/vomiting.

Norepinephrine and specific serotonin antidepressant (NaSSA) Example: Remeron (mirtazapine) Example: Remeron (mirtazapine) Indirectly increasing synaptic norepinephrine and serotonin through blockade of central presynaptic alpha2-adrenergic receptors. Indirectly increasing synaptic norepinephrine and serotonin through blockade of central presynaptic 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, nausea/vomiting than SSRIs. Causing less insomnia, sexual dysfunction, 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 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; may improve sexual dysfunction associated with chemotherapy and hormonal therapy. Causing less sexual dysfunction than SSRIs; may improve sexual dysfunction associated with chemotherapy and hormonal therapy. Additional benefit for smoking cessation. Additional benefit for smoking cessation. Side effects: insomnia, tachycardia, seizure. Side effects: insomnia, tachycardia, seizure.

Other serotonin modulators Example: Mesyrel (trazodone) Example: Mesyrel (trazodone) Inhibiting serotonin reuptake; blocking histamine (H1) and alpha1-adrenergic receptors. Inhibiting serotonin reuptake; blocking histamine (H1) and alpha1-adrenergic receptors. Usually used as a hypnotic ( mg/d) rather than an antidepressant ( mg/d). Usually used as a hypnotic ( mg/d) rather than an antidepressant ( mg/d). Decreasing number of awakenings, increasing total sleep time and percentage of deep sleep (stages 3+4). Decreasing number of awakenings, increasing total sleep time and percentage of deep sleep (stages 3+4). Side effects: sedation, hypotension, dizziness. Side effects: sedation, hypotension, dizziness.

Pharmacotherapy for insomnia Mesyrel (trazodone) is the drug of choice. Mesyrel (trazodone) is the drug of choice. Be careful of sedative and muscle- relaxing effects of benzodiazepines. Avoid using them in patients with BPSD. Be careful of sedative and muscle- relaxing effects of benzodiazepines. Avoid using them in patients with BPSD.

Conclusion BPSD should be appropriately treated. BPSD should be appropriately treated. Consider Non-pharmacological treatment first. Reserve pharmacotherapy for the second line. Consider Non-pharmacological treatment first. Reserve pharmacotherapy for the second line. Medication for each patient should be individually taylored. Risk and benefit should be carefully assessed. Medication for each patient should be individually taylored. Risk and benefit should be carefully assessed. Consult the psychiatrist when the problem becomes obvious and out of control. Consult the psychiatrist when the problem becomes obvious and out of control.

Thank you for attention