TCAs (Tricyclic Anti-Depressants) were developed in the early 1950s during the birth of psychopharmacology.  In December 1950, chlorpromazine was synthesized from synthetic antihistamines.  By 1955, this antipsychotic was generating substantial revenue as the first widely used psychiatric drug. At this time, the serotonin theory of depression had not yet been developed, and psychotherapy was a relatively new concept. The first TCA reported for the treatment of depression was imipramine. Patients who were prescribed imipramine to treat other medical problems reported disasterous side effects of mania.  This led to testing the drug on depressed patients.  In 1957, following several trials, the antidepressant effect of imipramine was reported.  Many TCAs have since been replaced by newer forms of anti-depressants (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs)) with fewer and less intense side effects. However, TCAs are still considered highly effective and are prescribed for the treatment of depressive disorders.

Most TCAs work in the same way SNRIs do, in that they block the serotonin and norepinephrine transporters, thus relieving anxiety and depression.  Primarily, tricyclic anti-depressants are used in the clinical treatment of mood disorders including major depressive disorder (MDD), post-traumatic stree disorder (PTSD), bipolar disorder (BD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD).  TCAs have also shown effectiveness in treating several different types of chronic pain, such as fibromyalgia and neuropathic pain.

Common physiological side effects include dry mouth, constipation, blurry vision, dizziness, sweating, muscle dysfunction, irregular heart rhythms, nausea, vomiting, drowsiness, urinary retention and increased body temperature.  Psychological side effects include cognitive and/or memory impairment, anxiety, confusion and restlessness.

Toxic effects caused by overdose can include delirium, hallucinations, coma and twitching.  An overdose from TCAs is extremely fatal due to their cardiovascular and neurological toxicity and their ability to be quickly absorbed into the small intestine.  Unfortunately, it can take several hours for the symptoms of a TCA overdose to appear.

According to the US government classification of psychiatric medications, TCAs are considered “non-abusable.”  However, there have been cases reported where TCAs are used recreationally in combination with other drugs such as methadone or alcohol.  These combinations can be deadly.

TCAs may produce what is called a “discontinuation syndrome.”  It has been decided by the medical profession that the term “withdrawal” is a term associated with drugs of abuse like opioids.  Therefore, discontinuation symptoms may include anxiety, malaise, motor disturbance, insomnia, headaches and/or nausea.