aripiprazole

As a CNS depressant, aripiprazole has the potential to enhance the adverse or toxic effects of other CNS depressants, such as cannabis.

The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

ALL OPIOIDS: As a CNS depressant, aripiprazole has the potential to enhance the adverse or toxic effects of other CNS depressants, such as opioids. 

METHADONE: a) Concomitant administration with the related medication risperidone resulted in decreased clearance of risperidone and increased serum levels.

ALL OPIOIDS: The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive. 

METHADONE: Methadone is a moderate CYP2D6 inhibitor. Like risperidone, aripiprazole is a CYP2D6 substrate.

ALL OPIOIDS: While the additive effects may be clinically appropriate, monitoring of the patient is advised. It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness. 

METHADONE: Concomitant use of methadone with aripiprazole may enhance the adverse/toxic effects of aripiprazole. However, to what extent methadone inhibits the metabolism of aripiprazole is unclear. Patients should be monitored for the appearance of adverse drug effects and counselled on avoidance, if possible, of methadone while taking aripiprazole.

AMPHETAMINE: Amphetamine-induced stimulatory effects may be reduced by antipsychotics. 

a) A case report of 2 individual children receiving aripiprazole and stimulants experienced uncontrolled movements (dystonia), which seemed to occur upon abrupt discontinuation of the stimulant. 

b) 7 adults who reported recreational amphetamine use in the past year were given aripiprazole 15mg daily. Aripiprazole seemed to diminish positive subject-rated effects (enjoyed the drug, willing to take again) of low-dose amphetamines, but not high dose amphetamines. Aripiprazole also reduced self-administration of methamphetamine. 

c) In a double-blind, placebo-controlled, randomized trial of 90 methamphetamine-dependent adults given aripiprazole, there was a reduction in methamphetamine-positive urine screens. However, this reduction also occurred in the placebo arm and was not statistically significant.

METHYLPHENIDATE: Concomitant use of antipsychotics and methylphenidate may enhance each other's adverse or toxic effects. 

The risk of creating extreme hyper- or hypodopaminergic states appears to be greatest when adjusting the dose of one class of medication in the setting of the other. When used with a stimulant, consider antipsychotic switching without cross-tapering. 

a) Antipsychotic medications cause post-synaptic up-regulation of dopamine receptors over time. Removing the antagonism on these hypersensitive dopamine receptors while simultaneously increasing synaptic dopamine levels by an indirect agonist could cause an extreme hyperdopaminergic state. 

b,c) The mechanism of reduced abuse-related effects of methamphetamine via aripiprazole is unknown.

AMPHETAMINE: The effectiveness of amphetamines may be diminished when aripiprazole is co-administered. Patients should be monitored upon initiation of one of these drugs and during dosage changes. 

a) Abrupt discontinuation of stimulant treatment may result in emergence of extrapyramidal side effects due to removal of the anticholinergic effects of the stimulant. Conversely, sudden discontinuation of aripiprazole can result in severe dyskinesias. When used concurrently, stimulant and antipsychotic dosages should be tapered gradually before discontinuation. 

b,c) Aripiprazole, given in a controlled and monitored setting, may have some benefit in attenuating the positive reinforcement effects of methamphetamine.

METHYLPHENIDATE: If concomitant use is clinically appropriate, patients should be monitored for adverse or toxic effects of both aripiprazole and methylphenidate when initiating therapy or during dose changes. 

KETAMINE: a) As a CNS depressant, aripiprazole has the potential to enhance the adverse or toxic effects of other CNS depressants, such as ketamine.  

b) A 34 year old male presented with agitation, altered mental status, hypertension, and tachycardia. Urine tests confirmed he recently used cannabis and ketamine. He was given the related drug paliperidone which led to symptom resolution.

PHENCYCLIDINE: Novel antipsychotic agents such as aripiprazole may block the psychotomimetic effects of phencyclidine.

KETAMINE: a) The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.  

b) Antipsychotics can attenuate the effects of NMDA antagonists such as ketamine.

KETAMINE:  a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness. 

b) Some people may have a milder ‘high’ with ketamine if they are also taking aripiprazole.

PHENCYCLIDINE: Some people may have a milder 'high' with phencyclidine if they are also taking aripiprazole.