PSYCHOTROPIC

Medications AND THEIR

SIDE EFFECTS

Laura Kho Sui San

Pharmacist

Hospital Sentosa

OUTLINE Introduction Types of PSYCHOTROPIC drugs Antipsychotics Antidepressants Mood Stabilizers Sedative/Hypnotics Medications for Dementia

Common SIDE EFFECTS CNS side effects Systemic/Metabolic side

effects Demand and supply

What are

PSYCHOTROPIC Medications?

PSCYHOTROPIC Medications

Medications that act on the Central Nervous System (CNS)

Mood

Behavior Consciousness

Cognition Perception

PSCYHOTROPIC Medications

Treat SYMPTOMS of mental illness

Antipsychotics

Antidepressants Mood stabilizers

Anxiolytics Sedatives Hypnotics

Dementia ……

Treat symptoms of PSYCHOSIS Hallucinations

Delusions Disorganized behavior, etc

PSYCHOSIS usually caused by too much

DOPAMINE in the brain

Antipsychotics

BLOCK dopamine

receptors in the brain

TYPICAL and ATYPICAL antipsychotics

CHLORPROMAZINE

PERPHENAZINE TRIFLUOPERAZINE

HALOPERIDOL

SULPIRIDE

FLUPHENAZINE FLUPENTIXOL

ZUCLOPENTIXOL

RISPERIDONE

QUETIAPINE

PALIPERIDONE

AMISULPRIDE

OLANZAPINE

CLOZAPINE

ARIPRIPAZOLE

RISPERIDONE

LONG-ACTING

INJECTION PALIPERIDONE

LONG-ACTING

INJECTION

Depo injections : Fluphenzine (Modecate®), Fluphenthixol (Fluanxol®), Risperidone (Consta®), Paliperidone (Sustena®)

Once every one to four weeks

Inject into deltoid or gluteal muscle.

Released slowly into the body

Ensure adherence

Antipsychotics

• Used to treat DEPRESSION

• Also used to treat other conditions, including

Generalised Anxiety Disorder (GAD), Panic Disorder, Obsessive-Compulsive Disorder (OCD)

HOW DO THEY WORK?

• Theory: Increase levels of neurotransmitters like serotonin and noradrenaline

• Improve mood and emotion

NOT INSTANT FIX!

May take up to 4-6 weeks to start

working

Selective Serotonin Reuptake Inhibitors (SSRI)

1st -line

Effective and less side effects

ESCITALOPRAM

(LEXAPRO®) 10MG

SETRALINE

(ZOLOFT®) 50MG

FLUOXETINE

(PROZAC®) 20MG

FLUVOXAMINE

(LUVOX®) 50MG,

100MG

Which SSRI to choose?

Efficacy is similar If one SSRI fails, try another SSRI

Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)

Similar to SSRIs

Designed to work better than SSRI because they also affect noradrenaline levels

Only use if SSRIs do not work

DULOXETINE

(CYMBALTA®)

30MG, 60MG

VENLAFAXINE

(EFEXOR XR®)

75MG, 150MG

Tricyclic Antidepressants (TCAs)

Old

Effective but NOT 1st choice

Many side effects such as dry mouth, constipation, sedation, weight gain especially in elderly

TOXIC IN OVERDOSE

Examples : AMITRIPTYLINE, IMIPRAMINE, DOTHIEPINE, CLOMIPRAMINE

OTHERS

Noradrenegic and Specific Serotonergic Antidepressant (NaSSA)

Mirtazapine (Remeron®) 15mg, 30mg (orodispersible tablet)

Monoamine Oxidase Inhibitors

Moclobemide (Aurorix®) 150mg

Not popular

Need for monitoring, many drug-drug, drug-food interactions.

Control emotion and behaviour

Mania (“high”) and to prevent both episodes of mania and depression in bipolar disorder

Mood symptoms like depression and aggression in schizophrenia

Behavioral problems in mental retardation

Mr Hamid comes to the pharmacy with a prescription for T. Sodium Valproate

400mg BD and T. Olanzapine 5mg ON. Is Mr Hamid suffering from epilepsy?

+

Sodium Valproate (Epilim®) 200mg

Carbamazepine 200mg, 400mg

Lamotrigine 50mg, 100mg

Lithium 300mg

Not common

Selected patients need to be quite well educated.

Narrow therapeutic index – risk of toxicity

Sedatives / Hypnotics

INSOMNIA (SLEEP)

WORRY

ANXIETY AGGRESSION /

AGITATION

Benzodiazepines (BDZ)

Clonazepam (Rivotril®, Klonopin®)

Lorazepam (Ativan®)

Alprazolam (Xanax®)

Diazepam (Valium®)

Z compound (Non-benzodiazepine)

– Zolpidem (Stilnox®)

SEDATIVE/ HYPNOTIC

For sleep :

– INDUCE sleep : Zolpidem

– MAINTAIN sleep : benzodiazepines

– Choice of BDZ depends on onset of action and length of action

For anxiety :

– Usually but not always alprazolam (short-acting)

For aggression/agitation :

– BDZ : intermediate- to long-acting like clonazepam, diazepam, lorazepam

SEDATIVE/ HYPNOTIC

USE SHORT TERM!

• TOLERANCE : need MORE and MORE BDZ to achieve the required effect

• How fast does tolerance develop?

• Hypnotic effects (more rapidly)

• Anxiolytic effects (more slowly)

• Depends on dose, potency and duration of therapy

• After 4-6 months of REGULAR use, become less effective

• If you suddenly stop or reduce dose → WITHDRAWAL SYMPTOMS

PROBLEMS with BDZ : TOLERANCE and DEPENDENCE

Short-term use of BDZ: Less than 4 weeks OR intermittent courses (e.g. EOD)

• Most types of dementia are PROGRESSIVE, cannot be cured e.g. Alzheimer’s disease

• BUT, medicines may prevent symptoms from getting worse for a period of time.

• Early to middle stages of the disease.

• Not everyone will benefit from medication.

Cholinesterase inhibitors

Donepezil (Aricept®) tablets 10mg

Rivastigmine (Exelon®)

Capsules 1.5mg, 3mg

Patch 4.6mg/24hr and 9.5mg/24hr

NMDA-antagonist

– Memantine (Ebixa®) tablets 10mg, 20mg

Are the side effects from my medicines making me sicker?

Or am I feeling ill because of my disease?

WHAT ARE THE COMMON

SIDE EFFECTS OF PSYCHOTROPIC MEDICINES?

COMMON SIDE EFFECTS

CNS

• ExtraPyramidal

Symptoms(EPS)

• SLEEP disturbances

• SEIZURES

Systemic / Metabolic

• Metabolic syndrome

• Hypersalivation

• AntiCHOLINERGIC side effects

• Cardiovascular

• Agranulocytosis

EXTRAPYRAMIDAL SYMPTOMS (EPS)

EXTRAPYRAMIDAL SYMPTOMS (EPS)

Higher risk in typical antipsychotics e.g.

haloperidol and

trifluoperazine.

PSYCHOSIS usually caused by too much

DOPAMINE in the brain

Antipsychotics

BLOCK dopamine

receptors in the brain

TYPICAL and ATYPICAL antipsychotics

EXTRAPYRAMIDAL SYMPTOMS (EPS)

• Acute dystonia • Pseudoparkinsonism • Tardive dyskinesia (TD) • Akathisia

EXTRAPYRAMIDAL SYMPTOMS (EPS)

3 situations

Start new antipsychotic (Rapidly)Increase dose of antipsychotic

Reduce dose of anticholinergic

DOSE-RELATED

Acute DYSTONIA

“Sudden, involuntary muscle contractions or spasms.”

Acute dystonia

Uprolling eyeballs Head and neck twisted to one side.

Start oral new

antipsychotic

IM / IV e.g.

IM Haloperidol

Within

days/hours

Within

minutes

More common in : Young males New patients Those treated with older

drugs

Acute DYSTONIA

Management of DYSTONIA

ACUTE : Give anticholinergic drugs

IM or orally. Usually IM Procyclidine

(Kemadrin®) 5mg stat Usually effective within 20

minutes.

Occasionally, 2nd or 3rd injections are necessary; they should be administered at half hour intervals. CONTINUE with Tab. BENZHEXOL

for prophylaxis

Pseudoparkinsonism

“Adverse effect of drug that causes symptoms

resembling parkinsonism.”

Reversible

Can be mistaken for negative symptoms of schizophrenia.

Mask-like face

Management of

Pseudoparkinsonism

REDUCE dose

SWITCH to another

antipsychotic

Tab. BENZHEXOL for treatment and prophylaxis. (Review

use after 3 months)

Tardive Dyskinesia (TD)

“Repetitive, involuntary, purposeless movements.”

“Worsen under stress.”

Grimacing Tongue

protrusion Lip smacking Excessive eye

blinking Choreiform hand

movements (e.g. pill rolling)

Tardive dyskinesia

Can lead to difficulty breathing, eating or speaking!

More common in : Elderly females Prior history of

acute EPS earlier in treatment

Tardive Dyskinesia (TD)

The result of PROLONGED use or HIGH-

DOSE antipsychotics

Management of Tardive

Dyskinesia (TD)

REDUCE to lowest

possible dose

SWITCH to another

antipsychotic (e.g. clozapine)

Tab. BENZHEXOL can WORSEN TD!

AKATHISIA

“A feeling of

INNER RESTLESSNESS”

Akathisia

Foot stamping when seated

Constantly pacing up and down

Rocking from foot

to foot

Management of AKATHISIA

REDUCE dose SWITCH to another

antipsychotic

Low-dose beta-blocker. eg

propranolol 20-80 mg/day

Benzodiazepines

ANTICHOLINERGICS – How to handle

side effects from ANTIPSYCHOTICS?

Oral: Benzhexol 2mg (Artane®) Only if patients are on antipsychotics

ALWAYS QUERY if there is

BENZHEXOL but NO injection or oral ANTIPSYCHOTIC

IM : Kemadrin® (Procyclidine) Acute / emergency situation KPK item

SLEEP

SLEEP

PSYCHIATRIC

DRUGS

Sedating

Activating Insomnia

Restlessness

Somnolence Daytime sedation

Examples of sedating and activating drugs

↓↓Sedating

Clozapine Chlorpromazine

Olanzapine Quetiapine

Fluvoxamine Benzodiazepines

↑↑Activating

Fluoxetine Sertraline

Benzhexol Aripriprazole

How to Manage …?

Somnolence

Reduce dosage.

Change to single bedtime dose.

Switch to less

sedating alternative

Insomnia Take in the

daytime Switch to less

activating alternative if cannot tolerate.

SEIZURES

All antipsychotics have the risk of ing seizure threshold o Psychotic disorders, depression and OCD

may also seizure threshold

Highest risk : CHLOPROMAZINE and

CLOZAPINE (high dose)

MONITOR, MONITOR, MONITOR …… Prophylaxis : Anticonvulsant

(SODIUM VALPROATE)

COMMON SIDE EFFECTS

CNS

• ExtraPyramidal

Symptoms(EPS)

• SLEEP disturbances

• SEIZURES

Systemic / Metabolic

• Metabolic syndrome

• Hypersalivation

• AntiCHOLINERGIC side effects

• Cardiovascular

• Agranulocytosis

METABOLIC

METABOLIC

(

Insulin RESISTANCE

↑ blood sugar

Weight GAIN ˃5% Of initial weight

DYSLIPIDEMIA

↑ cholesterol, LDL and mostly TGs

METABOLICCommon in ATYPICAL ANTIPSYCHOTICS

CLOZAPINE

OLANZAPINE

QUETIAPINE

Ref: American Diabetes Association. Consensus development conference on antipsychotic drugs and

obesity and diabetes. Diabetes Care 2004;27:596-601

MANAGEMENT Monitor, monitor, monitor…….

MANAGEMENT Monitor, monitor, monitor……. (as per

protocol)

Lifestyle modifications

If weight gain >5% of initial weight, suggest switching to another weight-neutral AP. e.g. Aripriprazole

OPTION: (up to

2g/day has been studied)

Decrease body weight Improve metabolic abnormalities

METFORMIN

Hypersalivation

Antipsychotics

esp CLOZAPINE

HYPERSALIVATION • Drooling, especially at night

• Usually at initiation

• May reduce in severity over time but may also persist

How to Manage?

BENZHEXOL (Take before 7pm for

nighttime relief) DAYTIME : CHEW sugarless gum to

aid swallowing

Hyperprolactinaemia

Serum prolactin ˃ 25mcg/L

(10-25 mcg/L) Not always symptomatic

Gynecomastia Galactorrhea Menstrual abnormalities Sexual dysfunction

Hyperprolactinaemia

REDUCE dose SWITCH drug AUGMENT with aripriprazole

Potent D2 blockers: Haloperidol Risperidone Paliperidone Amisulpiride

ANTICHOLINERGIC SIDE EFFECTS

• Common culprits :

ANTICHOLINERGIC SIDE EFFECTS

ANTIPSYCHOTICS Clozapine

Chlopromazine

ANTICHOLINERGIC

AGENTS Benzhexol

Benztropine

TRICYCLIC

ANTIDEPRESSANTS Amitriptyline Clomipramine

Dothiepine Imipramine

Constipation Urinary Retention

Other peripheral side effects (eg dry mouth,

blurred vision) Confusion, memory impairment and delirium

CONSTIPATION Usually persists after chronic usage of AP

↓ed gastric motility

CLOZAPINE

Clozapine-induced GI hypomotility syndrome,

bowel ischemia, intestinal obstruction.

Prevention and Treatment

of CONSTIPATION

Lifestyle modifications: HIGH-FIBRE diet,

adequate fluid intake and exercise.

Stool softeners, bulk-forming laxatives and stimulants (can use in

combination) Lactulose, bisacodyl tablets, Ravin

enema.

AVOID combining constipating drugs

(BENZHEXOL)

Urinary Retention

Urinary hesitation or retention Peripheral anticholinergic side effect

Can result in secondary overflow incontinence,

enuresis, an increased risk of urinary tract infection or sepsis.

Management of Urinary Retention

Urinary hesitancy / retention: Rule out UTI and structural defects Minimize dose of culprit drug(s) AVOID combining drugs with

anticholinergic activity

Incontinence / euresis : Monitor fluid intake Void bladder before bed Limit diuretic use (caffeine, alcohol)

Confusion

Ranges from impaired concentration,

memory impairment, attention deficits and confusion.

May worsen delirium.

AVOID use in the

ELDERLY.

Cardiovascular Side Effects Postural Hypotension Tachycardia Cardiac Arrhythmia

Postural Hypotension “A systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least

10 mmHg within three minutes of standing.” *

Common : (α1-adrenergic

antagonism ) Chlorpromazine, clozapine, quetiapine

* American Academy of Neurology

Management of Postural Hypotension

Tell the patient to RISE SLOWLY from a lying or sitting position.

Maintain adequate fluid intake Tilt the head of the bed at night. Divide or decrease the dose of the culprit

drug Use support stockings.

Tachycardia Heart rate is over 100 bpm.

Dose-dependent More common in MALE and younger

patients.

How to manage tachycardia ? Start LOW and go SLOW ß-blockers (propranolol 10-

80mg/day) may help

Cardia Arrythmia

All antipsychotics can contribute to prolongation of QT interval

Dose-dependent Incidence of sudden cardiac death ~ 2x

HIGHER among patients taking AP Do baseline ECG and monitor regularly

OTHER SERIOUS BUT

RARE SIDE EFFECTS

CLOZAPINE and AGRANULOCYTOSIS

CLOZAPINE • Age • Female • Asian

Agranulocytosis ~ 1%

Within 3 months of starting treatment

Upon initiation, weekly WBC for the 1st six months, 2-weekly for the next six

month and thereafter, monthly.

WBC < 3.50 ×

109per L

ANC < 1,500 cells per mm3

CLOZAPINE and AGRANULOCYTOSIS

If ↓ing trend in TWBC, REFER If TWBC <3.5 × 109per L, REFER If heart rate ˃100 bpm, REFER

ALL MEDICINES HAVE SIDE EFFECTS.

BUT NOT EVERYONE WILL SUFFER FROM SIDE EFFECTS.

Thank You…