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Antipsychotics

3.12 Important drug interactions

Concomitant administration of an antipsychotic with a drug which is sedative (eg alcohol) or which reduces blood pressure (eg ACE inhibitor) can increase the potential for these effects.

Many antipsychotic drugs have the potential to affect heart rhythm; the risk of arrhythmia is increased when such an antipsychotic drug is combined with other drugs that affect rhythm or drugs that increase the concentration of the antipsychotic (eg azole antifungal drugs). Drugs which reduce serum potassium can increase the risk of adverse effects arising from QT-interval prolongation. The table below lists common drugs that can interact to prolong the QT interval; a comprehensive list of drugs that prolong the QT interval should be consulted where necessary.

Rarely, antipsychotics can reduce white cell and red cell count; concomitant use with other drugs that interfere with bone-marrow function (myelosuppressants) might increase the risk of reducing blood cells and, possibly, platelets.

Consult summaries of product characteristics and other sources of information on the interactions of individual antipsychotics

Interacting drug or drug class

Effect of interaction

Risk-reduction measures

ACE inhibitors and angiotensin-II receptor antagonists1

Increased hypotensive effect

Monitor blood pressure and ask about postural hypotension

Alcohol

Increased sedation

Warn patient of excessive sedation and of psychomotor impairment

Amantadine

Increased risk of extrapyramidal effects2

Amphotericin

Hypokalaemia increases risk of adverse effects of QT-interval3 prolongation

Ensure any hypokalaemia is corrected

Anaesthetics, general

Increased hypotensive effect

Monitor blood pressure and ask about postural hypotension

Anti-arrhythmics with QT-interval prolonging properties (eg amiodarone, disopyramide, flacainide, and sotalol)

Increased risk of QT-interval4 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Antidepressants, tricyclic

Increased risk of arrhythmias Antimuscarinic5 effects, especially of phenothiazine antipsychotics, increased

Antidepressants, tricyclic and SSRIs

Increased risk of seizures

Citalopram and escitalopram

Increased risk of QT-interval6 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Antiepileptics

Epilepsy control may be impaired

Antihistamines7, sedative

Increased sedation

Select non-sedative antihistamine; warn patient of excessive sedation and of psychomotor impairment

Anxiolytic and hypnotic drugs (eg benzodiazepines)

Increased sedation

Warn patient of excessive sedation and of psychomotor impairment

Atomoxetine

Increased risk of QT-interval8 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Beta-blockers

Increased hypotensive effect

Monitor blood pressure and ask about postural hypotension

Calcium-channel blockers

Increased hypotensive effect

Monitor blood pressure and ask about postural hypotension

Clonidine

Increased hypotensive effect

Monitor blood pressure and ask about postural hypotension

Corticosteroids9

Hypokalaemia increases risk of adverse effects of QT-interval10 prolongation

Increased risk of metabolic effects such as weight gain and diabetes

Ensure any hypokalaemia is corrected

Diuretics (loop and thiazide)

Hypokalaemia increases risk of adverse effects of QT-interval prolongation

Increased hypotensive effect

Ensure any hypokalaemia is corrected

Monitor blood pressure and ask about postural hypotension

Dopamine agonists11 (eg drugs used for Parkinson’s disease)

Antipsychotics inhibit antiparkinsonian effects of dopamine agonists

Lithium

Increased risk of neuroleptic malignant syndrome, extrapyramidal side effects and CNS toxicity

If concomitant administration necessary, adjust dose so plasma-lithium concentration is at minimum effective level; monitor closely for side effects

Methadone

Increased risk of QT-interval12 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Macrolide antibiotics (eg erythromycin, clarithromycin)

Increased risk of QT-interval13 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Metoclopramide

Increased risk of extrapyramidal effects14

Moxifloxacin

Increased risk of QT-interval15 prolongation

Preferably avoid concomitant use of drugs that prolong QT interval

Opioid analgesics

Increased hypotensive and sedative effect

Monitor blood pressure and ask about postural hypotension; warn patient of excessive sedation and of psychomotor impairment

Tramadol

Increased risk of seizures

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15


  1. A substance that binds to a receptor but produces no effect and inhibits an agonist from binding to the receptor
  2. Extrapyramidal symptoms or side effects describe movement disorders such as acute dystonia, parkinsonian effects, akathisia and tardive dyskinesia; these effects result from disturbance—by dopamine antagonists—of the extrapyramidal system, which is responsible for involuntary reflexes and coordination of movement. (The voluntary movement system runs through the ‘pyramidal pathways’ of the medulla of the brain)
  3. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  4. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  5. Reduction or blocking of the effects of parasympathetic nerves; antimuscarinic effects include dry mouth, difficulty swallowing, blurred vision, confusion, palpitations, constipation, and urine retention
  6. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  7. A substance that blocks the effects of histamine. Histamine is released when the body mounts an immune response; also, histamine is a neurotransmitter and it regulates the functioning of the gastrointestinal system. Of the histamine receptors; histamine H1 receptor is involved in immune reactions, motion sickness and sleep regulation, while histamine H3 receptor is activated by histamine acting as a neurotransmitter
  8. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  9. Substances that mimic effects of hormones produced by the adrenal cortex. The term corticosteroids covers glucocorticoids (steroids which reduce inflammation) and mineralocorticoids (steroids which act on the kidneys to retain sodium and water and promote excretion of potassium)
  10. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  11. A chemical substance that binds to a receptor and mimics the effect of the physiological (endogenous) substance binding to the receptor
  12. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  13. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes
  14. Extrapyramidal symptoms or side effects describe movement disorders such as acute dystonia, parkinsonian effects, akathisia and tardive dyskinesia; these effects result from disturbance—by dopamine antagonists—of the extrapyramidal system, which is responsible for involuntary reflexes and coordination of movement. (The voluntary movement system runs through the ‘pyramidal pathways’ of the medulla of the brain)
  15. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes