Lofepramine (antidepressant): uses, indications and side effects
The tricyclic antidepressants are a group of drugs used in the treatment of depressive symptoms.
Lofepramine is one of them: this drug exerts its therapeutic effect on mood through the inhibition of several neurotransmitters, mainly norepinephrine and serotonin. But like the vast majority of tricyclic antidepressants, it is not exempt from adverse reactions and side effects.
In this article we explain what lofepramine is and how it works., what medical uses it has, what are its main side effects and contraindications, as well as its clinical efficacy compared to other similar antidepressants.
- Recommended article: "Types of depression: its symptoms, causes and characteristics"
Lofepramine: characteristics and clinical uses
Lofepramine is a drug that belongs to the group of tricyclic antidepressants. It was developed by Leo Pharmaceuticals, a Swedish pharmaceutical company, and marketed in the years eighties as a treatment for depression, under the trade names of Gamanil, Lomont, Tymelyt, among others.
Tricyclic antidepressants have been used for decades to relieve mood disturbances and depressive symptoms, but have now been replaced by another class of antidepressants with fewer side effects, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (IRSN).
It has been suggested that lofepramine might act largely as a prodrug (an inactive compound that, once metabolized, becomes active substance) of desipramine, another tricyclic antidepressant drug that acts mainly by inhibiting the reuptake of norepinephrine. As with the vast majority of tricyclic antidepressants, monoamine reuptake inhibition (serotonin, dopamine, norepinephrine, etc.) is the way in which they exert their therapeutic effect.
The initial therapeutic dose of lofepramine is usually 70 mg twice daily.. Although, in general, the dose is increased gradually and the patient can take between 140 mg and 210 mg daily. This drug does not have addictive potential like other tricyclic antidepressants (eg. eg amineptine) and does not cause sedation. Some activating effect may be experienced early in lofepramine treatment, something some depressed patients find unpleasant.
Mechanism of action
Lofepramine is a potent and selective inhibitor of the reuptake of norepinephrine and a moderate serotonin reuptake inhibitor. It also acts as a weak antagonist of acetylcholine receptors. (those of the muscarinic type). This medication has fewer anticholinergic and antihistamine properties than amitriptyline, one of the classic tricyclic antidepressants.
As we have previously discussed, lofepramine is extensively metabolized to desipramine; however, this fact is unlikely to play a substantial role in its overall effects, as this antidepressant exhibits a lower toxicity and anticholinergic side effects relative to desipramine, while retaining clinical efficacy equivalent.
Following oral administration, the drug is rapidly absorbed and peak plasma concentrations of lofepramine and desipramine are reached in 1 hour and 4 hours, respectively. The plasma elimination half-life of this antidepressant is quite short; however, the long elimination half-life of desipramine (12 to 24 hours) may lead to accumulation of the drug with repeated administration, an aspect to take into account when starting the treatment.
Side effects
The most frequent adverse reactions after the use of tricyclic antidepressants include: anxiety, agitation, insomnia, abnormal sensations or paraesthesia, low blood pressure, dizziness, irritability and confusion.
These symptoms are shared by lofepramine, which may also cause the following side effects of its own (the frequency of which is not known with certainty).
1. digestive effects
Among the most common digestive effects are constipation, diarrhea, dry mouth, nausea, changes in the sense of taste or smell, and vomiting.
2. cardiovascular effects
Effects on the heart after taking lofepramine may include: arrhythmias, changes in the electrocardiogram (the graphical representation of electrical activity of the heart as a function of time), an abnormal heart rhythm, heart block, sudden cardiac death, and heart rate high.
3. blood disorders
Although the frequency of these blood disturbances is unknown, abnormal blood cell counts, sugar changes, and low blood sodium levels can occur.
4. breast effects
Continued use of lofepramine can cause breast enlargement, even in men. In addition, there may also be a spontaneous secretion of breast milk that is not related to lactation or pregnancy.
5. Effects on the skin
The use of lofepramine can also cause skin disorders such as: abnormal or excessive sweating, hair loss, hives, itching, increased sensitivity to light, and rashes.
6. Cognitive and psychiatric alterations
Mental effects include hallucinations, delusions, migraines, mania and hypomania, seizures, and suicidal behavior.
7. other effects
Other adverse reactions include: appetite changes, blurred vision, difficulty emptying the bladder, slurred speech (when not being able to move the muscles needed to articulate words), liver problems, tinnitus (ringing in the ears), sexual dysfunction (p. eg impotence), swelling and weight changes.
contraindications
To use lofepramine with caution it is recommended to pay attention to the following contraindications:
Cardiovascular diseases
narrow angle glaucoma
Kidney or liver failure
In the recovery period after a myocardial infarction
In arrhythmias (especially heart block)
Mania
People being treated with amiodarone or terfenadine
clinical efficacy
In clinical trials, lofepramine has been shown to be an effective antidepressant, with an onset of action of less than 2 weeks when administered in doses up to 210 mg per day to patients with different types of depression.
Double-blind controlled studies have shown that its overall antidepressant efficacy is significantly greater than placebo, and comparable to that of imipramine, amitriptyline, clomipramine, maprotiline, and mianserin.
In three studies that were carried out over 6 weeks, involving depressed patients, lofepramine produced reductions in the scores of the scale of Hamilton depression of approximately 60%, which were similar to those produced by imipramine and amitriptyline, and greater than those produced by clomipramine. In addition, the results of two non-comparative multicenter studies carried out in 4 weeks, concluded that lofepramine has significant anxiolytic efficacy, in addition to its properties antidepressants.
Finally, it is worth pointing out another 6-week double-blind randomized study in which paroxetine was compared with lofepramine in the treatment of 138 patients with major depressive disorder. The results showed that the antidepressant efficacy of lofepramine was comparable to that of paroxetine in the treatment of patients depressed and similar improvements were obtained in both groups in the mean total scores of the Montgomery-Asberg scale for the depression.
Bibliographic references:
Lancaster, S. G., & González, J. Q. (1989). Lofepramine. Drugs, 37(2), 123-140.
Moon, C. A., & Vince, M. (1996). Treatment of major depression in general practice: a double-blind comparison of paroxetine and lofepramine. The British journal of clinical practice, 50(5), 240-244.
Robertson, M. M., Abou-Saleh, M. T., Harrison, D. A., Nairac, B. L., Edwards, D. R. L., Lock, T.,... & Katona, C. L. AND. (1994). A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. Journal of Psychopharmacology, 8(2), 98-103.
Siwers, B., Borg, S., d'Elia, G., Lundin, G., Forshell, G. P., Raotma, H., & Roman, G. (1977). Comparative clinical evaluation of lofepramine and imipramine: pharmacological aspects. Acta Psychiatrica Scandinavica, 55(1), 21-31.
