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Prescription Anxiety Medications (cont.)

Medical Editor:

What are some drug interactions for anti-anxiety drugs?


Alprazolam increases blood levels of the antidepressants imipramine and desipramine. Alprazolam may also interact with some calcium channel blockers and with grapefruit juice. Carbamazepine decreases blood levels of alprazolam.

Combining benzodiazepines with alcohol or other central nervous system depressants can cause increased sedation and potentially dangerous respiratory depression.

Fluoxetine, propoxyphene, and oral contraceptives increase blood levels of alprazolam (Xanax), as do ketoconazole, itraconazole, nefazodone, fluvoxamine, and erythromycin.

Oral antifungal agents such as ketoconazole and itraconazole may significantly decrease blood levels of clonazepam (Klonopin).

Serious side effects, including respiratory arrest, may occur if lorazepam (Ativan) is combined with clozapine. Dosage of lorazepam should be halved when taken with valproate or probenecid.

Theophylline and aminophylline may affect the sedative effects of lorazepam.

Several drugs can increase the blood levels of triazolam (Halcion), including isoniazid, oral contraceptives, and ranitidine. Ketoconazole, itraconazole, and nefazodone have a profound effect on triazolam metabolism and should not be taken with it. Grapefruit juice also increases the amount of triazolam in the blood.

Triazolam may interact with calcium channel blockers, antidepressants, ergotamine, amiodarone, and cyclosporine.

Selective Serotonin Reuptake Inhibitors

SSRIs should not be used with MAOIs. Additionally, serotonin syndrome may occur if SSRIs are administered with triptan migraine drugs, linezolid (Zyvox), St. John's Wort, lithium, or tramadol. Combining SSRIs with aspirin, other nonsteroidal anti-inflammatory drugs, or warfarin, increases the risk of bleeding.

Levels of imipramine and desipramine have been shown to significantly increase when taken with certain SSRIs. Combining SSRIs with antipsychotic drugs may result in neuroleptic malignant syndrome, a serious side effect.

Citalopram (Celexa) may cause a significant rise in blood levels of desipramine and other tricyclic antidepressants.

Taking fluoxetine (Prozac) with pimozide or thioridazine is contraindicated because of possibly dangerous effects on heart rhythm. Stable levels of phenytoin and carbamazepine may rise to toxic levels if fluoxetine is introduced.

Plasma levels of pimozide, thioridazine, alosetron, astemizole, cisapride, diazepam, and tizanidine increased significantly when used with fluvoxamine (Luvox). Consequently, these drugs should not be used together. Additionally, dosage adjustments may be required for warfarin, mexiletine, and theophylline when used with fluvoxamine.

Paroxetine (Paxil) should not be used with pimozide or thioridazine because of possibly dangerous effects on heart rhythm. Digoxin, atomoxetine, risperidone, and theophylline levels may require adjustment when given with paroxetine.

Sertraline (Zoloft) should not be used with pimozide because of the potential for severe cardiac effects.

Vilazodone may cause eye pain, visual changes, and swelling in the ocular area.

Vilazodone and vortioxetine can affect sodium blood levels and coagulation of blood.

Tricyclic Antidepressants (TCAs)

TCAs should not be used with MAOIs. SSRIs may increase blood levels of TCAs, as may cimetidine. Phenytoin and barbiturates may decrease blood levels of TCAs. Anticholinergic drugs may worsen some side effects of TCAs.

Decongestants and other drugs containing catecholamines should not be used with TCAs. The sedative effect of TCAs may be enhanced by alcohol and other CNS depressant drugs.


MAOIs interact with a wide range of prescription and nonprescription medications, including other antidepressants, anticonvulsants, antihistamines and decongestants, as well as some foods. Many of these interactions can be fatal. Patients should inform all those involved in their care if they are using MAOIs.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs should not be used with MAOIs.

Heavy alcohol use with duloxetine (Cymbalta) may result in liver injury.

Other Antidepressants

Bupropion (Wellbutrin) should not be used with the MAOI phenelzine. Use caution when bupropion is taken with drugs known to lower the seizure threshold (for example, theophylline or steroids). Use of bupropion with nicotine transdermal systems may result in hypertension.

HIV drugs (such as ritonavir), as well as oral antifungals (for example, ketoconazole) increase plasma levels of trazodone (Desyrel). Carbamazepine reduces blood levels of trazodone. Blood levels of phenytoin and digoxin increased when given with trazodone.


Antihistamines may cause increased drowsiness when used with CNS depressants.

Buspirone (BuSpar)

Large amounts of grapefruit juice may increase blood levels of buspirone. Other drugs that affect blood levels of buspirone include oral antifungals, calcium channel blockers, certain antibiotics (Erythromycin and Rifampin), and nefazodone (Serzone).


Gabapentin (Neurontin) may affect blood levels of hydrocodone and morphine. Gabapentin levels can decrease when given with the antacid Maalox. Allow 2 hours between the drugs.

The following medications significantly decrease blood levels of lamotrigine (Lamictal): oral contraceptives, phenobarbital, primidone, phenytoin, carbamazepine, oxcarbazepine, and rifampin.

The following medications decrease topiramate (Topamax) levels: phenytoin, carbamazepine, valproic acid, and lamotrigine. Using topiramate with acetazolamine or dichlorphenamide may increase the risk for kidney stones. Topiramate can interact with some drugs used for diabetes (metformin, pioglitazone), so careful blood sugar monitoring is warranted when they are combined.

The following drugs may significantly increase levels of valproate (Depakote) in the blood: aspirin and felbamate. The following drugs may significantly decrease blood levels of valproate: rifampin, carbapenem antibiotics (imipenem, meropenem, ertapenem).


Beta-blockers used with other cardiac drugs -- calcium channel blockers, anti-arrhythmics, ACE inhibitors, digitalis -- may result in additive effects on blood pressure and heart rate, sometimes to a dangerous level.

Warfarin concentrations increase when used with propranolol.

Hypotension and cardiac arrest have occurred with use of haloperidol and propranolol.


Sedation may increase if clonidine (Catapres) and guanfacine (Tenex) are used with other CNS depressants, including alcohol.


Increased drowsiness may occur when aripiprazole (Abilify) is given with other CNS-active drugs. Significant increases in blood levels may occur if given with oral antifungals (ketoconazole). A significant decrease in blood level of aripiprazole may occur if given with carbamazepine.

Ziprasidone (Geodon) should not be used with other drugs known to cause prolongation of the QT interval, such as thioridazine and chlorpromazine.

The effect of blood pressure-lowering medications may be enhanced when taken with either ziprasidone or risperidone (Risperdal). These medications may decrease the effectiveness of levodopa/dopamine agonists. Increased drowsiness may occur if these drugs are combined with other CNS depressants.

Carbamazepine may decrease blood levels of ziprasidone and risperidone; ketoconazole may increase levels of ziprasidone.

The following drugs may significantly increase blood levels of quetiapine (Seroquel): oral antifungals (ketoconazole), certain antibiotics (erythromycin), and protease inhibitors (indinavir). Phenytoin and thioridazine may significantly decrease blood levels of quetiapine.

Olanzapine (Zyprexa) should be used with caution with other CNS depressant drugs and alcohol. The following drugs may increase blood levels of olanzapine: fluvoxamine, fluoxetine, rifampin, and omeprazole. Carbamazepine may decrease blood levels of olanzapine. Orthostatic hypotension potential may rise if olanzapine is used with diazepam or alcohol, and olanzapine can enhance blood pressure-lowering effects of other drugs.

Medically Reviewed by a Doctor on 5/4/2016

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