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Medical Author:

Mary L Windle, PharmD

Pharmacy Editor:

Omudhome Ogbru, PharmD

Omudhome Ogbru, PharmD

Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

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Tell the doctor what medications are currently being taken because many medicines interact with TCAs. Do not take any nonprescription or herbal medications without first consulting the doctor or pharmacist. The following are examples of interactions, but they do not represent a complete list.

• TCAs may increase the blood levels and/or risk of toxicity of the following medications:
  • MAOIs (These may cause serious and sometimes fatal reactions; some TCAs have been used safely with MAOIs, but the dose of TCAs must be increased very slowly and the person must strictly adhere to MAOI dietary restrictions.)
  • Sympathomimetics such as pseudoephedrine (Sudafed)
• The following substances may increase the toxicity of TCAs:
  • Alcohol or other drugs that depress the central nervous system such as medications taken for insomnia
  • Medications, such as antihistamines (Benadryl), that may produce similar side effects
  • Antifungal medications such as ketoconazole (Nizoral) or fluconazole (Diflucan)
  • SSRIs, venlafaxine (Effexor, Effexor XR), and nefazodone [(Serzone) may increase risk for serotonin syndrome—symptoms include hypertension, fever, muscle tremor, or confusion]
  • tramadol (Ultram) (may increase risk of seizures)
  • Medications such as cisapride, thioridazine, quinidine, antihistamines, erythromycin, dofetilide, and pimozide that also increase the risk for abnormal heart rhythm
  • valproic acid (Depakote, Depakote ER, Depakene, Depacon)
• Other interactions include the following:
  • TCAs may decrease the ability for clonidine (Catapres) to lower blood pressure levels.

  • carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol) may decrease TCA effectiveness.

  • St. John's wort may decrease TCA effectiveness and increase the risk of serotonin syndrome.

Side Effects: This is NOT a complete list of possible side effects reported with TCAs. A doctor, health care provider, or pharmacist can discuss a more complete list of side effects.

• Confusion, agitation, or hallucinations (Contact a doctor immediately if these occur.)
• Severe diarrhea, fever, sweating, muscle stiffness, or tremors (These may be symptoms of neuroleptic malignant syndrome. Contact a doctor immediately.)
• Rapid or abnormal heartbeat or fainting (Contact a doctor immediately if these occur.)
• Changes in sexual interest or ability
• Manic episodes in persons with bipolar disorder (If not combined with a mood-stabilizing medication, SSRIs may induce manic episodes in individuals with bipolar disorder [manic depression].)
• Drowsiness (Caution is advised when operating machinery, driving, or performing other tasks that require alertness.)
• Photosensitivity (increased risk of sunburn) (Use protective clothing, such as long sleeves and hats, and sunscreen to decrease the risk of sunburn.)
• Rash
• Nausea
• Dry mouth
• Urine retention
• Blurred vision
• Constipation
• Lightheadedness when standing up from a sitting or lying position (Stand up gradually from lying down or sitting positions.)
• Seizures (TCAs lower the threshold for seizures, that is, seizures may occur more easily in the person taking TCAs. Caution is advised for individuals prone to seizures or those who have a history of seizures.)

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