With this post, we continue our sort-of-biweekly series on medications used to treat bipolar disorder and related symptoms. Several weeks ago, we covered Wellbutrin (bupropion), an antidepressant that’s in a class of its own. This week, we turn our attention to an older class of medications used to treat depression – Tricyclics.

Medications in this group work differently from SSRI’s (including Prozac and Paxil), SSNRI’s (including Effexor and Cymbalta), and Wellbutrin. While tricyclics have fallen out of favor since the introduction of the newer generation of antidepressants, they remain effective and may be useful alternatives in some cases.

Tricyclic Antidepressants

Tricyclics (so called due to a three-ring chemical structure) inhibit the re-absorption (reuptake) of serotonin, norepinephrine, and (to a lesser extent) dopamine, increasing their availability to brain cells. Tricyclics include the following medications:

  • Amitriptyline
  • Amoxapine
  • Desipramine (Norpramin)
  • Doxepin (Sinequan)
  • Imipramine (Tofranil, Tofranil-PM)
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)

Tricyclic antidepressants are effective agents for treating depression and many types of anxiety disorders. However, in individuals with bipolar disorder, tricyclics present a risk of manic switching – quite possibly a higher risk than with more recent agents such as SSRI’s. The tricyclics also have some “niche” uses, including treating insomnia, migraine headaches and some chronic pain syndromes, bedwetting, and ADHD.

Potential Side Effects

Tricyclics also affect a number of other brain chemicals, such as histamine, possibly causing many of the side effects attributed to this class of antidepressants, including (in some cases)…

  • Manic switching
  • Agitation and suicidal ideation
  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Dizziness
  • Impaired sexual functioning
  • Increased heart rate
  • Disorientation or confusion
  • Headache
  • Low blood pressure
  • Sensitivity to sunlight
  • Increased appetite
  • Weight gain
  • Nausea
  • Weakness

Because of this somewhat overwhelming side-effect profile, doctors typically try tricyclics only when other antidepressants, such as Prozac and Cymbalta, are ineffective or not well tolerated.

Important: Tricyclics are generally contraindicated for people with untreated narrow-angle glaucoma, enlarged prostate, or certain types of heart disease (due to a higher risk of heart attack), or heart-rhythm abnormalities. Tricyclics can also affect blood sugar levels, so if you have diabetes, your doctor may instruct you to check your blood sugar levels more often. If you have a history of seizures or thyroid problems, use tricyclics cautiously, if at all.

Tricyclics in My Practice

When I was training in psychiatry, tricyclics were still the most widely used antidepressants, as the SSRI family of medicines was just starting to appear in the US. They were effective and often well tolerated but could have many side effects. People often felt a little druggy and sedated on them, at least for a while. In my current practice, I rarely use tricyclics unless other options have been ineffective or not tolerated. I have a few people on them who benefit from the medication making them feel sleepy. A few of my patients take low doses specifically for sleep.

In the 70’s and 80’s tricyclics were popular alternatives to stimulants for treating ADHD in children. But after a number of reports of sudden death in children on tricyclics, these medications rapidly fell out of favor and are almost never used in children anymore.

A few people I work with are on low dose tricyclics to treat migraine headaches – the neurologists will sometimes use these medicines for headache and other pain-management situations.

Remember: Any antidepressant can take 2-3 weeks or even longer to become fully effective, and it may take several weeks to work up to a therapeutic dose, so your depression may not lift for several weeks. Patience is key. Give the medication a few weeks to become effective and give your body a few weeks to adjust to it. Any negative side effects you experience are likely to fade over time.
Schedule an appointment to follow up with your doctor 3-4 weeks after you start taking the medication, but don’t hesitate to call earlier if you’re concerned about the medication’s effectiveness or any side effects you may be experiencing.

If you’ve taken any tricyclics for bipolar depression or other conditions or are a doctor who has prescribed any of the antidepressants in this class, please share your experiences, insights, and observations.