Imipramine

Depression -For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. One to three weeks of treatment may be needed before optimal therapeutic effects are evident. Childhood Enuresis -May be useful as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older, after possible organic causes have been excluded by appropriate tests. In patients having daytime symptoms of frequency and urgency, examination should include voiding cystourethrography and cystoscopy, as necessary. The effectiveness of treatment may decrease with continued drug administration.

• Depression Lower dosages are recommended for elderly patients and adolescents
• Lower dosages are also recommended for outpatients as compared to hospitalized patients who will be under close supervision
• Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance
• Following remission, maintenance medication may be required for a longer period of time, at the lowest dose that will maintain remission
• Usual Adult Dose: Hospitalized patients -Initially, 100 mg/day in divided doses gradually increased to 200 mg/day as required
• If no response after two weeks, increase to 250 to 300 mg/day
• Outpatients -Initially, 75 mg/day increased to 150 mg/day
• Dosages over 200 mg/day are not recommended
• Maintenance, 50 to 150 mg/day
• Adolescent and Geriatric Patients -Initially, 30 to 40 mg/day; it is generally not necessary to exceed 100 mg/day
• Childhood Enuresis Initially, an oral dose of 25 mg/day should be tried in children aged 6 and older. Medication should be given one hour before bedtime
• If a satisfactory response does not occur within one week, increase the dose to 50 mg nightly in children under 12 years; children over 12 may receive up to 75 mg nightly
• A daily dose greater than 75 mg does not enhance efficacy and tends to increase side effects
• Evidence suggests that in early night bedwetters, the drug is more effective given earlier and in divided amounts, i.e., 25 mg in midafternoon, repeated at bedtime. …

• Safety and effectiveness in the pediatric population other than pediatric patients with nocturnal enuresis have not been established ( see BOX WARNING and WARNINGS: Clinical Worsening and Suicide Risk )
• Anyone considering the use of imipramine hydrochloride in a child or adolescent must balance the potential risks with the clinical need
• The safety and effectiveness of the drug as temporary adjunctive therapy for nocturnal enuresis
• In pediatric patients less than 6 years of age has not been established. …

In the literature, there were four well-controlled, randomized, double-blind, parallel group comparison clinical studies done with imipramine hydrochloride in the elderly population. There was a total number of 651 subjects included in these studies. These studies did not provide a comparison to younger subjects. There were no additional adverse experiences identified in the elderly. …

• Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with imipramine hydrochloride and should counsel them in its appropriate use
• A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available for imipramine hydrochloride
• The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. …

• The concomitant use of monoamine oxidase inhibiting compounds is contraindicated
• Hyperpyretic crises or severe convulsive seizures may occur in patients receiving such combinations
• The potentiation of adverse effects can be serious, or even fatal
• When it is desired to substitute imipramine hydrochloride in patients receiving a monoamine oxidase inhibitor, as long an interval should elapse as the clinical situation will allow, with a minimum of 14 days. …

Drugs Metabolized by P450 2D6 : The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). …

Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. …

Note- Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when imipramine hydrochloride is administered. Cardiovascular : Orthostatic hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, ECG changes, precipitation of congestive heart failure, stroke. Psychiatric : Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis. …

Pregnancy Animal reproduction studies have yielded inconclusive results (see also ANIMAL PHARMACOLOGY & TOXICOLOGY .) There have been no well-controlled studies conducted with pregnant women to determine the effect of imipramine hydrochloride on the fetus. However, there have been clinical reports of congenital malformations associated with the use of the drug. …

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic overdose. Therefore, hospital monitoring is required as soon as possible. Children have been reported to be more sensitive than adults to an acute overdosage of imipramine hydrochloride. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.