Psychotropic Medications & Their Side Effects
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Transcript of Psychotropic Medications & Their Side Effects
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…