Polypharmacy refers to the use of multiple medications in one individual. Medications, whether for blood pressure or depression, do not work in a vacuum. When we swallow, inhale, or inject medications they make their way through our bodies in complex ways. Most medications are transported in blood attached to proteins, but many others are transported unattached in their free form. As medications make their way to their target organs, they come in contact with all kinds of tissues, cells, and fluids before they are metabolized and/or eliminated from the body.
Prescribing multiple medications for one individual increases the risk for adverse drug interactions. Some medications might displace a medicine from transport proteins while others might alter the activity of enzymes, such as CYP450 enzymes, that metabolize other drugs. Alternatively, some medications might compete with other drugs at their receptor sites and alter their effects.
While the variety of mechanisms are beyond the scope of this post, we review some of the most common drug interactions for medications used to treat mental health disorders.
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 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
Common Side Effects of Antiretroviral Drugs
|Nucleoside Reverse Transcriptase Inhibitors (NRTIs)||Neuropsychiatric Side Effects|
|Abacavir||Depression, Mania, Suicidal ideation, Anxiety|
|Psychosis, Insomnia, Nightmares, Fatigue|
|Didanosine||Nervousness, Agitation, Mania, Lethargy|
|Emtricitabine||Depression, Odd dreams, Insomnia, Confusion, Irritability|
|Interferon-a-2a||Depression, Suicidal ideation, anxiety, mania, psychosis, insomnia, delirium, altered cognition|
|Lamivudine||Depression, Insomnia, Dizziness, dystonia|
|Zidovudine||Anxiety, Agitation, Restlessness, Insomnia, Mania, Psychosis|
|Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)|
|Delavirdine||Anxiety, Agitation, Amnesia,|
|Efavirenz||Anxiety, Insomnia, Irritability, Depression|
|Suicidal ideation, psychosis, Nightmares, Vivid dreams|
|Nevirapine||Vivid dreams, Nightmares, Visual hallucinations|
|Delusions, Mood Instability|
|Rilpivirine||Odd Dreams, Insomnia, lightheadedness/dizziness|
|Indinavir||Anxiety, Agitation, Insomnia|
|Lopinavir and Ritonavir||Insomnia|
|Nelfinavir||Depression, Anxiety, Insomnia|
|Ritonavir||Anxiety, Agitation, Euphoria|
|Hallucinations, Taste changes|
|Saquinavir||Anxiety, Agitation, Euphoria|
|Raltegravir||Depression, suicidal ideation, psychosis|
|Vivid dreams, nightmares, vertigo,|
|Elvitegravir||Depression, Insomnia, Suicidal ideation|
Drug Interaction Tables
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