Drug Interactions

Simply Psych EDU's

Drug-Drug Interactions

Important Drug-Drug Interactions


Valproic acid (VPA) + Lamotrigine:

  • Valproic acid (VPA) increases lamotrigine levels
  • Increases risk of Steven-Johnson’s Syndrome (SJS/TEN)
  • When using both, decrease the dose of lamotrigine by 50%


Carbamazepine (CBZ) is an inducer of CYP3A4:

  • CBZ induces its own metabolism
  • CBZ induces the metabolism of numerous other medications including oral contraceptives, clozapine, alprazolam, buspirone, and clonazepam


Lithium + NSAIDs (not aspirin), ACE Inhibitors, Thiazide diuretics, low sodium diet:

  • Increases lithium levels


Lithium + caffeine, theophylline, high sodium diet:

  • Decreases lithium levels


Grapefruit Juice

  • Grapefruit juice is a potent inhibitor of CYP3A4 and P-glycoprotein
  • Grapefruit juice increases blood levels of many medications metabolized by CYP3A4


Smoking Tobacco cigarettes:

  • Induces activity of CYP1A2
  • The induction does not appear to be from the nicotine, but from the hydrocarbons in smoke
  • Decreases blood levels of medications metabolized by CYP1A2 (Olanzapine, Clozapine, Caffeine)



  • Increased risk of hypertensive crisis when eating tyramine containing foods while taking MAOIs, SSRIs, TCAs, Pseudoephedrine, and Stimulants
  • Tyramine-rich foods include banana peel, beer, fava beans, aged cheese, sauerkraut, sausage, soy sauce, concentrated yeast extract.


Fluoxetine, Paroxetine, and Bupropion are potent inhibitors of CYP2D6:

  • They can raise blood levels of medications metabolized by CYP2D6.
  • Tamoxifen and Codeine are prodrugs requiring metabolism by CYP2D6. Efficacy of these drugs may be decreased when used with inhibitors of CYP2D6.


Antimicrobial-Psychotropic Drug Interactions:

  • Antimalarials: Increase phenothiazine (e.g. chlorpromazine) levels
  • Azoles: Increase alprazolam, midazolam, and buspirone levels
  • Clarithromycin, Erythromycin: Increase alprazolam, midazolam, carbamazepine, clozapine, and buspirone levels
  • Quinolones: Increase clozapine and benzodiazepine levels but decreases benzodiazepine effects
  • Isoniazid: Increases haloperidol and carbamazepine levels. Isoniazid + disulfiram can cause ataxia
  • Linezolid: Serotonin syndrome if used with serotonergic drugs


Other Interactions/Adverse Reactions:

  • Erythromycin, Clarithromycin, and Ketoconazole: QT prolongation and ventricular arrythmias with TCAs and antipsychotics
  • Linezolid is an irreversible MAO-A inhibitor: Serotonin syndrome and Hypertensive crisis
  • Isoniazid is a weaker MAO inhibitor: Reports of Serotonin syndrome and hypertensive crisis



Nucleoside Reverse Transcriptase Inhibitors (NRTIs)Neuropsychiatric Side Effects
AbacavirDepression, Mania, Suicidal ideation, Anxiety
Psychosis, Insomnia, Nightmares, Fatigue
DidanosineNervousness, Agitation, Mania, Lethargy
EmtricitabineDepression, Odd dreams, Insomnia, Confusion, Irritability
Interferon-a-2aDepression, Suicidal ideation, anxiety, mania, psychosis, insomnia, delirium, altered cognition
LamivudineDepression, Insomnia, Dizziness, dystonia
ZidovudineAnxiety, Agitation, Restlessness, Insomnia, Mania, Psychosis
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
DelavirdineAnxiety, Agitation, Amnesia,
EfavirenzAnxiety, Insomnia, Irritability, Depression
Suicidal ideation, psychosis, Nightmares, Vivid dreams
NevirapineVivid dreams, Nightmares, Visual hallucinations
Delusions, Mood Instability
EtravirineInsomnia, lightheadedness/dizziness
RilpivirineOdd Dreams, Insomnia, lightheadedness/dizziness
Protease Inhibitors
AtazanavirDepression, Insomnia
IndinavirAnxiety, Agitation, Insomnia
Lopinavir and RitonavirInsomnia
NelfinavirDepression, Anxiety, Insomnia
RitonavirAnxiety, Agitation, Euphoria
Hallucinations, Taste changes
Decreased libido
SaquinavirAnxiety, Agitation, Euphoria
Depression, Hallucinations
Excessive dreaming
Integrase Inhibitors
RaltegravirDepression, suicidal ideation, psychosis
Vivid dreams, nightmares, vertigo,
ElvitegravirDepression, Insomnia, Suicidal ideation
DolutegravirInsomnia, Fatigue
Fusion Inhibitors
EnfuvirtideDepression, Insomnia

Lithium Toxicity

Lithium ToxicityCausesPresentation Treatment
OverdoseNauseaHold/Discontinue Lithium
DehydrationVomitingMonitor lithium levels every 2-4 hours
Hyponatremia (low sodium)DiarrheaIntravenous (IV) Fluids
Low GFR (Glomerular Filtration Rate)AtaxiaHemodialysis recommended if Lithium level >2.5 mEq/L with signs of neurotoxicity
Renal Impairment/Failure/DiseaseConfusionHemodialysis recommended if no improvement with IV fluids
Drug InteractionsTremorHemodialysis recommended if Lithium level >4.0 mEq/L
Diuretics (except loop diuretics)Slurred Speech
NSAIDs (except aspirin)Seizures
ACE Inhibitors Abnormal Movements

Lithium Level Monitoring

Lithium MonitoringTarget Lithium LevelRecommended Labs
Acute Mania0.8-1.2mEq/LBaseline: CBC, CMP, Cr, BUN, TSH, Weight, EKG (in pts>50yo or with cardiac disease)
Maintenance0.6-1.0 mEq/LAfter 1 week, 1 month, 6 months, and 12 months of starting lithium: Lithium Level, TSH, BUN/Cr, Electrolytes, monitor weight
Every 6-12 months: Lithium Level, TSH, BUN/Cr, Electrolytes, monitor weight
NOTE: Check Lithium levels after 4-5 half lives (blood should be collected prior to next dose); Also check lithium levels after dosage changes, addition of other drugs, or if suspecting toxicity