Lofepramine (antidepressant): Uses, Indications And Side Effects
Tricyclic antidepressants are a group of drugs used to treat depressive symptoms.
Lofepramine is one of them: this medication 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 free of 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 effectiveness compared to other similar antidepressants.
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 1980s as a treatment for depression, under the trade names Gamanil, Lomont, Tymelyt, among others.
Tricyclic antidepressants have been used for decades to relieve mood disturbances and depressive symptoms, although they have now been replaced by another class of antidepressants with fewer side effects, such as serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).
It has been suggested that lofepramine may act largely as a prodrug (an inactive compound that, once metabolized, becomes an active substance) of desipramine, another tricyclic antidepressant drug that acts primarily by inhibiting norepinephrine reuptake. . As with the vast majority of tricyclic antidepressants, inhibition of the reuptake of monoamines (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, generally, the dose is increased gradually and the patient can take between 140 mg and 210 mg daily. This drug does not have an addictive potential like other tricyclic antidepressants (e.g. amineptine) and does not cause sedation. At the beginning of treatment with lofepramine a certain activating effect may be experienced, something that some depressed patients find unpleasant.
Mechanism of action
Lofepramine is a potent and selective norepinephrine reuptake inhibitor 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 mentioned previously, lofepramine is extensively metabolized into desipramine; However, this is unlikely to play a substantial role in its overall effects, as this antidepressant exhibits lower toxicity and anticholinergic side effects relative to desipramine, while retaining equivalent clinical efficacy.
After oral administration, the drug is rapidly absorbed and maximum plasma concentrations of lofepramine and desipramine are achieved within 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 drug accumulation with repeated administration, an aspect to consider when initiating treatment.
Side effects
The most common adverse reactions after the use of tricyclic antidepressants include: anxiety, agitation, insomnia, abnormal sensations or paresthesia, arterial hypotension 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).
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 graphic representation of the electrical activity of the heart versus time), an abnormal heart rhythm, heart block, sudden cardiac death, and high heart rate .
3. Blood disorders
Although the frequency of these blood disorders is unknown, abnormal blood cell counts, sugar changes, and low blood sodium levels may occur.
4. Breast effects
Continued consumption of lofepramine can cause breast enlargement, even in men. In addition, spontaneous secretion of breast milk that is not related to lactation or pregnancy can also occur.
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: changes in appetite, blurred vision, difficulty emptying the bladder, difficulty speaking (not being able to move the muscles needed to articulate words), liver problems, tinnitus (ringing in the ears), sexual dysfunction (e.g. e.g. impotence), bloating and weight changes.
Contraindications
To use lofepramine with caution, it is recommended to pay attention to the following contraindications:
Clinical efficacy
In clinical trials, lofepramine has been found to be an effective antidepressant, with an onset of action of less than 2 weeks when administered in doses of up to 210 mg per day to patients with various 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 6-week studies involving depressed patients, lofepramine produced reductions in Hamilton Depression Scale scores of approximately 60%, which were similar to those produced by imipramine. and amitriptyline, and greater than those produced by clomipramine. Furthermore, the results of two non-comparative multicenter studies carried out over 4 weeks concluded that lofepramine has significant anxiolytic efficacy, in addition to its antidepressant properties.
Finally, we should point out another six-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 depressed patients and similar improvements were obtained in both groups in the mean total scores of the Montgomery-Asberg scale for depression.
