Butriptyline: characteristics, uses and side effects

Butriptyline is a drug with a good level of efficacy against the symptoms of depression.

Antidepressant drugs comprise a range of medications used for the treatment of depressive symptoms and behavioral disturbances associated with low mood. Within the category of antidepressants is the group of tricyclics, among which are butriptyline, a drug that differs from the other tricyclics due to its peculiar mechanism of action..

In this article we explain what butriptyline is and what tricyclic antidepressants consist of, what the mechanism of action of this drug is, what type of side effects it causes, and what its clinical efficacy is, compared with other similar drugs.

What is butriptyline?

Buttriptyline is a drug of the tricyclic Antidepressant group, chemically related to amitriptyline and imipramine.. It is a drug that has been used in several European countries, including Spain, in the treatment of depression. Because its pharmacological action is somewhat different from that of other tricyclic antidepressants, it has been described as an "atypical" or "second generation" drug.

Since its development in 1974 by Wyeth (formerly known as American Home Products), one of the world's largest pharmaceutical companies, and its subsequent marketing in the United Kingdom, it was rarely dispensed compared to other antidepressant drugs in the same group. It was marketed under the brand names Evadene, Evasidol, Evadyne and Centrolese.

Although butriptyline has been considered an antidepressant drug of the tricyclic group, its mechanism of action differs significantly from prototypical tricyclics such as imipramine or amitriptyline. Next, let us see what the mechanism of action of tricyclic antidepressants is, in order to compare them with that of butriptyline.

Tricyclic antidepressants

Tricyclic antidepressant drugs are used in the treatment of depressive disorders and other behavioral pathologies, as is the case with butriptyline. These drugs act as monoamine agonists.. Their main effects are on serotonin receptors, noradrenaline receptors and, to a lesser extent, dopaminergic receptors.

The therapeutic activity of tricyclic antidepressants is produced by the inhibition of the reuptake of these neurotransmitters, which leads to an increase in the availability of these monoamines in the synaptic cleft. However, these drugs also act, albeit secondarily, on histaminic and cholinergic (acetylcholine-related) receptors, exerting an antagonistic effect on them.

The mechanism of action of tricyclics is not very specific, since their therapeutic their therapeutic targets go beyond the most relevant neurotransmitter receptors and affect a number of other receptors.This means that, although they may be effective in alleviating depressive symptoms, they can also cause serious side effects and adverse reactions.

Mechanism of action

In in vitro studies, butryptiline has been shown to be a potent antihistamine and anticholinergic drug, with moderate antagonistic effects on the serotonergic 5-HT2 receptor and the α1-adrenergic receptor, and with very weak or negligible action as a noradrenaline reuptake inhibitor.

This mechanism of action seems to confer to this drug a profile very similar to that of the drugs iprindol and trimipramine, whose antagonistic effects on serotonin receptors could be responsible for their efficacy in improving mood.

However, in several clinical trials using similar doses, butriptyline has been found to be equally effective as amitriptyline and imipramine in treating depressive symptoms, despite the fact that these two antidepressant drugs have a more potent effect as 5-HT2 antagonists and serotonin-norepinephrine reuptake inhibitors.

It has been suggested that the mechanism of action of butryptiline is different from the other tricyclic antidepressants and that, perhaps, it functions as a prodrug, converting to an active metabolite once it is introduced into the body, thus acting with a different pharmacodynamics.

Side effects

Buttriptyline, as we have mentioned, is closely related to amitriptyline and has side effects similar to this tricyclic antidepressant. However, it appears that in the case of butryptiline, the sedation caused by its consumption is less, compared to other tricyclics, as well as the risk of drug interactions.

Since this drug has relatively weak effects as an α1 antagonist and practically nonexistent effects as a noradrenaline reuptake inhibitor, it has almost none of the antiadrenergic and adrenergic side effects.

Bottom line, the most prominent side effects and adverse reactions of butryptiline are related to the potent antihistaminic and anticholinergic effects it produces. it produces. The most common ones are presented below:

• Sedation (less than that of other tricyclic antidepressants, as we have discussed).
• Drowsiness.
• Dry mouth.
• Constipation.
• Urinary retention.
• Blurred vision.
• Cognitive / memory impairment.

Clinical efficacy

To evaluate the efficacy of a drug, it is usually compared with another drug from the same group and under appropriate experimental conditions. In this sense, in a multicenter study in which two experimental groups and a control group were randomly assigned under double-blind conditions, the efficacy of butriptyline versus amitriptyline was compared in a group of 77 patients aged 18 to 70 years and diagnosed with primary depression.

Butriptyline and amitriptyline were administered on an identical increasing schedule, up to 150 mg daily in the first week and a flexible schedule during the last 3 weeks of the trial. The mean daily doses were 145 mg butriptyline and 142 mg amitriptyline, after 2 weeks; and 77.5 mg amitriptyline and butriptyline, after 4 weeks. Nitrazepam (an anxiolytic hypnotic drug) and haloperidol (a conventional antipsychotic drug) were also allowed (if necessary).

Symptomatology and antidepressant efficacy of the drugs were assessed using the following tests: the Hamilton Depression Rating Scale, the General Depression Scale, the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI), as well as a side effect checklist.

After the initial comparison of the two treatment groups, the results showed that the antidepressant effects were significantly better with butriptyline with regard to the number of dropouts, in the total score and in the following factors of the General Depression Scale: depression, guilt, anxiety, somatization and somatic complaints. In addition, the frequency of haloperidol prescription was significantly lower in patients who were treated with butriptyline versus those who used amitriptyline.

The overall frequency of side effects and other parameters (hematological and biochemical variables, electrocardiogram, etc.) were the same in both groups. In conclusion, it was observed that butryptiline has the same indications as amitriptyline, but shows better antidepressant efficacy at the same dose, as well as greater relief of depression., as well as greater relief of anxiety, somatization and somatic complaints.

Bibliographical references:

• Brezinova, V.,Borrow, S., Oswald, I., Robinson, D. Effect of butryptyline on subjective feelings and sleep. Br J Clin Pharmacol. 1977 April; 4(2): 243-245. PMCID: PMC1429024. Last accessed June 11, 2008.
• Guelfi, J.D., Dreyfus, J.F., Delcros, M, Pichot, P. A double-blind controlled multicenter trial comparing butriptyline with amitriptyline (en inglés). Neuropsychobiology. 1983;9(2-3):142-6. PMID 6353270
• Kapadia, A. P., & Smith, S. M. (1976). A multi-centre general practitioner assessment of butriptyline hydrochloride ('Evadyne'). Current medical research and opinion, 4(4), 278-284.