Hypericum tricyclic antidepressants

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

St. John s wort (Hypericum perforatum) is a perennial wildflower indigenous to Europe, North Africa, and western Asia (Fig. 1) and has been used for medicinal purposes for over two millennia. As far back as the early 16th century, St. John s wort was used primarily to treat anxiety, depression, and sleep disorders. In the late 20th and early 21st century, St. John s wort has been recommended for the treatment of mild to moderate depression (7). In support of its use for the treatment of mild to moderate depression, a number of clinical trials have demonstrated that St. John s wort has comparable efficacy to the tricyclic antidepressants (i.e., imipramine) and selective serotonin reuptake inhibitors (e.g., fluoxetine and paroxetine) (8-13). 

Because suicide is one of the leading causes of death in elderly people and in other populations, rapid and effective treatment of depression is warranted. Current therapies include the use of electroconvulsive (shock) therapy, psychiatric intervention, and antidepressant drugs such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and serotonin-selective reuptake inhibitors (SSRIs). Recently, in the U.S., the use of St. John s wort (Hypericum perforatum) has become more prevalent, especially in the treatment of depression. 

Many patients with mild to moderate depression are aware of the potential benefits of the herbal remedy St. John s Wort (Hypericum perforatum). The active ingredients in the h3rpericum extract have yet to be identified and their mode of action is unclear, although it has been postulated that several of the known mechanisms of existing antidepressants are incorporated (inhibition of monoamine reuptake and the monoamine oxidase enzyme, as well as a stimulation of GABA receptors). Much of the original research into the efficacy of St. John s Wort was performed in Germany where its use is well established. Several direct comparisons with tricyclic antidepressants have shown equivalent rates of response but these studies should be interpreted with caution since many trials failed to... 

Tricyclic antidepressants are the mainstay of treatment of painful polyneuropathy, but cannot be used in a substantial number of patients. St. John s Wort (Hypericum perforatum) is a herbal antidepressant which may act via mechanisms similar to tricyclics. Clinical trials have extensively reported the ability of Hypericum perforatum extracts to exert a significant antidepressant activity [224-226], Hypericins, Fig. (13) are considered to be one of the compounds contributing to the activity of the extract [227], These... 

The REM (rapid eye movement) sleep latency decreased slightly under Hypericum treatment whereas the percentage of REM sleep remained unchanged. This is in contrast to well-known effects of tricyclic antidepressants which increase the latency while reducing the portion of REM sleep. The mean percentage of slow-wave sleep (stages 3 and 4) increased from 1.5 % to 6 % during Hypericum treatment (increase in 9 of 12 subjects), whereas it decreased from 4.1 % to 2.5 % with placebo (decrease in 7 of 12 subjects). This points to an improvement of sleep quality by Hypericum extract. 

To summarize, the EEG profile of Hypericum extract basically matches that of tricyclic antidepressants, while Hypericum extract appears to improve sleep quality without eliciting any signs of sedation. 

Czekalla and colleagues [271] looked for potential effects of Hypericum extract on cardiac conduction, since it is well-known that tricyclic antidepressants can delay atrioventricular conduction. Of 84 patients treated with the Hypericum extract LI 160 and 76 patients receiving imipramine in a therapeutic drug trial [253] evaluable ECG recordings were available at baseline and after 6 weeks of treatment. All patients suffered from a severe episode of recurrent depressive disorder [ICD-10 F 33.2] the daily doses were 3 x 600 mg LI 160 and 3 x 50 mg imipramine, respectively. 

Tricyclic antidepressants + St John s wort (Hypericum perforatum)... 

Future directions for research on hypericum may continue the work done in clinical efficacy. More specifically, studies may be of interest that examine its effects in treatment of more severe depression and different subtypes of depression. The comparative efficacy of different hypericum preparations could be further investigated, and optimum dosages need to be established (Linde et al. 1996). Further work is needed to compare hypericum s efficacy and side effects with those of the SSRIs or atypical antidepressants, because published studies to date have only compared it with tricyclics. 

For most of the reference-controlled trials, only the number of adverse events has been reported without distinguishing between suspected adverse drug reactions and events that were obviously not related to the study medication. In all the reference-controlled trials, the frequency of adverse events was substantially lower in the patient groups treated with Hypericum than in those treated with the reference substances. This holds in particular for the adverse reactions typically associated with tricyclic and, to a lesser degree, tetracyclic antidepressants, such as dry mouth, constipation, tiredness and drop of blood pressure. No specific risk profile for Hypericum could be derived from the reference-controlled studies. 

It may therefore be concluded that Hypericum extract is safe and well-tolerated with a frequency of adverse events noticeably similar to that of placebo, and distinctly below that of tricyclic and tetracyclic antidepressants. It can be considered as an advantage of Hypericum extracts that there is no need for a cautious dose-titration. Treatment can be started with the full effective dose, since there is no risk of significant dose-dependent adverse reactions. 

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