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Tofranil Side Effects

Generic Name: imipramine

Note: This page contains side effects data for the generic drug imipramine. It is possible that some of the dosage forms included below may not apply to the brand name Tofranil.

It is possible that some side effects of Tofranil may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to imipramine: oral capsule, oral tablet

As well as its needed effects, imipramine (the active ingredient contained in Tofranil) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking imipramine, check with your doctor immediately:

Incidence not known
  • Abdominal or stomach pain
  • agitation
  • blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain or discomfort
  • clay-colored stools
  • cold sweats
  • confusion about identity, place, and time
  • continuing ringing or buzzing or other unexplained noise in the ears
  • cough or hoarseness
  • dark urine
  • decrease in the frequency of urination
  • difficulty in passing urine (dribbling)
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • double vision
  • dry mouth
  • false beliefs that cannot be changed by facts
  • fast, pounding, or irregular heartbeat or pulse
  • feeling, seeing, or hearing things that are not there
  • feeling that others are watching you or controlling your behavior
  • feeling that others can hear your thoughts
  • fever with or without chills
  • flushed, dry skin
  • general feeling of tiredness or weakness
  • hearing loss
  • hostility
  • hyperventilation
  • inability to move the arms, legs, or facial muscles
  • irritability
  • itching or rash
  • lack of coordination
  • lethargy
  • loss of balance control
  • lower back or side pain
  • mood or mental changes
  • muscle spasm or jerking of all extremities
  • muscle trembling, jerking, or stiffness
  • nightmares
  • pain or discomfort in the arms, jaw, back, or neck
  • painful or difficult urination
  • pinpoint red or purple spots on the skin
  • rapid weight gain
  • redness of the face, neck, arms, and occasionally, upper chest
  • restlessness
  • seizures
  • shakiness and unsteady walk
  • slow speech
  • sore throat
  • stiffness of the limbs
  • stupor
  • sweating
  • swelling of the face, ankles, legs, or hands
  • talking, feeling, and acting with excitement
  • trouble sleeping
  • twisting movements of the body
  • uncontrolled movements, especially of the face, neck, and back
  • unusual behavior
  • unusual tiredness or weakness
  • weakness in the arms, hands, legs, or feet
  • yellow eyes or skin

If any of the following symptoms of overdose occur while taking imipramine, get emergency help immediately:

Symptoms of overdose
  • Bluish color of fingernails, lips, skin, palms, or nail beds
  • cold, clammy skin
  • decreased awareness or responsiveness
  • difficult or troubled breathing
  • disorientation
  • fast, weak pulse
  • hallucinations
  • irregular, fast, slow, or shallow breathing
  • severe sleepiness

Some imipramine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Incidence not known
  • Bigger, dilated, or enlarged pupils (black part of the eye)
  • black tongue
  • decreased interest or ability in sexual intercourse
  • difficulty having a bowel movement (stool)
  • enlargement of the breast
  • hives or welts
  • increase in sexual ability, desire, drive, or performance
  • increased sensitivity of the eyes to light
  • increased urge to urinate during the night
  • peculiar taste
  • redness or other discoloration of the skin
  • severe sunburn
  • swelling of the testicles
  • swelling of the breasts or breast soreness in both females and males
  • swollen, painful, or tender lymph glands on the side of the face or neck
  • unexpected or excess milk flow from the breasts
  • waking to urinate at night

For Healthcare Professionals

Applies to imipramine: compounding powder, intramuscular solution, oral capsule, oral tablet


One study has suggested that as many as 85% of treated patients may experience dry mouth.

Several cases of acute angle closure glaucoma have been attributed to the anticholinergic effects of imipramine (the active ingredient contained in Tofranil) [Ref]

Anticholinergic side effects have been reported in as many as 50% of patients taking imipramine and include dry mouth, blurry vision, constipation and urinary retention.[Ref]

Nervous system

Nervous system side effects are common. General stimulation (manifested by insomnia and subjective and objective evidence of increased activity) have been reported frequently. Drowsiness, lightheadedness, dizziness, sleep abnormalities, myoclonus, tinnitus, jitteriness, tremor, delirium, cognitive impairment (especially in the elderly), and seizures have also been reported.[Ref]

One study has suggested that as many as 34% of treated patients may develop myoclonus.

Some investigators have estimated an incidence of 4 to 5 imipramine- induced seizures per 1000 treated patients.

A case of the neuroleptic malignant syndrome has been reported in one patient taking neuroleptics whose imipramine was abruptly discontinued.

Nearly all selective serotonin reuptake inhibitors, mixed serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants cause sleep abnormalities to some extent. These antidepressants have marked dose-dependent effects on rapid eye movement (REM) sleep, causing reductions in the overall amount of REM sleep over the night and delays the first entry into REM sleep (increased REM sleep onset latency (ROL)), both in healthy subjects and depressed patients. The antidepressants that increase serotonin function appear to have the greatest effect on REM sleep. The reduction in REM sleep is greatest early in treatment, but gradually returns towards baseline during long-term therapy; however, ROL remains long. Following discontinuation of therapy the amount of REM sleep tends to rebound. Some of these drugs (i.e., bupropion, mirtazapine, nefazodone, trazodone, trimipramine) appear to have a modest or minimal effect on REM sleep.[Ref]


Cardiovascular side effects associated with imipramine (the active ingredient contained in Tofranil) can be clinically significant. Orthostatic hypotension, tachycardia, PR interval prolongation, QRS widening, other conduction abnormalities and malignant arrhythmias have been reported. Vasospasm involving the extremities has been reported rarely. One study has found the relative risk of myocardial infarction to be 2.2 times greater in patients receiving tricyclic antidepressants including imipramine.[Ref]

Both antiarrhythmic and proarrhythmic effects have been reported in association with tricyclic therapy. Caution should be exercised if imipramine must be used in patients with cardiovascular disease.[Ref]


Psychiatric side effects have included mania, hypomania, suicidal ideation, paradoxical aggressiveness, mental status changes, and worsening of other psychiatric illnesses.[Ref]


A study of 26,005 antidepressant users has reported 2.3 times more upper GI bleeding episodes with the use of non-SSRI's. Upper gastrointestinal tract bleeding was observed in 3.5 times more frequently in patients receiving imipramine (the active ingredient contained in Tofranil) [Ref]

Gastrointestinal side effects most frequently include dry mouth and constipation. Nausea, vomiting and diarrhea have also been reported. Fatal adynamic ileus has also been reported (usually during concomitant treatment with other psychotropic agents).[Ref]


Although imipramine (the active ingredient contained in Tofranil) is not addicting, withdrawal symptoms, including nervousness, anxiety, restlessness, akathisia, nausea, malaise, sweating and salivation have been reported after abrupt discontinuation.[Ref]


Genitourinary problems have included urinary retention and male and female sexual dysfunction.[Ref]

One study of patients treated with various antidepressants has reported that 16 of 29 patients treated with imipramine admitted to sexual dysfunction. Decreased libido, more time reaching orgasm and difficulty reaching orgasm were cited as the most common dysfunctions.[Ref]


Hematologic side effects have included rare instances of reversible agranulocytosis and eosinophilia.[Ref]


Endocrinologic side effects are rare and have included hypoglycemia and hyponatremia (in association with the syndrome of inappropriate secretion of antidiuretic hormone).[Ref]


Hepatic side effects are rare and have included elevated liver function tests, drug-induced hepatitis, and acute hepatic failure.[Ref]


All cases of alopecia have been reported in women. All patients reported resolution or improvement from the hair loss within several months of discontinuation of the drug.[Ref]

Dermatologic side effects include sweating most frequently. Urticaria, angioedema, pruritus, and hyperpigmentation have been reported more rarely. Several cases of alopecia have also been reported.[Ref]


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