Antidepressant hypericum

St. John s wort Hypericum Antidepressant and Usually mild. May May decrease efficacy of... 

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. 

The active components of the herbaceaous perennial plant Hypericum perforatum are antiinflammatory, antidepressive and healing agents, therefore, their analysis is of considerable importance for health care. Samples were prepared by extracting the dried flowering tops by hot methanol. RP-HPLC separations were performed in an ODS column (250 X 4.6 mm i.d. particle size 5 pm) thermostated at 30°C. The steps of gradient elution are listed in Table 2.49. 

Although the individual inhibition of either MAO or COMT may be comparatively minor in isolation, their combined inhibition along with other monoamine or nonmonoamine actions could have additive if not synergistic effects. For example, a fraction with combined hypericin and flavonoids had antidepressant effects in an animal model (Butterweck et al. 1997). Hypericum is a particular case wherein a single isolated principle may be sufficient for the desired effect, but less effective than the entire plant extract. 

Another action of hypericum constituents that is particularly relevant to antidepressant effects is the ability to inhibit neuronal reuptake of monoamines. The half-maximal inhibition for monoamine uptake is 100 times lower than for the inhibition of MAOA or MAOB (Chatterjee et al. 1998a). Hyperforin is the major contributor to this action, blocking reuptake of 5-HT, norepinephrine, and dopamine (Muller et al. 1998). Half-maximal inhibition occurs at nanomolar concentrations (80 to... 

Antidepressant effects Hypericum has been shown to have antidepressant effects in several animal models. An extract fraction high in naphthodianthrones showed antidepressant effects in the forced-swim test, and was attenuated by a dopamine antagonist (sulpiride) (Butterweck et... 

Studies in mice have shown a hypericum extract to increase exploration in an unfamiliar environment, prolong sedative sleep time, and antagonize the effects of reserpine. Other antidepressant-like effects are found on the water-wheel test, and chronic administration decreased aggression in socially isolated male mice (Okpanyi and Weischer 1987). 

Pharmaceutical Comparison. At least 8 studies to date have examined the effectiveness of hypericum compared to the pharmaceutical antidepressants imipramine, amitriptyline, and maprotiline. Preliminary results indicate that hypericum is equivalent to standard antidepressants in effectiveness (Linde et al. 1996 Vorbach 1997). Similar to the pharmaceutical antidepressants, there is a 10-14 day lag for therapeutic effects of hypericum (Harrer et al. 1994). Indeed, the differences seen between hypericum and placebo groups becomes apparent between 2 and 4 weeks (Sommer and Harrer 1994). Hypericum has been reported to have a more favorable side-effect profile than several pharmaceutical antidepressants as well (Vorbach et al. 1994 Harrer et al. 1994). In double-blind studies, subjects have reported fewer and less-severe side effects. Although these initial results are promising, Linde and colleagues (1996) have concluded that the present evidence is inadequate to establish... 

Hypomania and use with other antidepressants One case has been reported of concurrent use of hypericum with an SSRI. Gordon (1998) reported a case of a 50-year-old woman taking 600 mg/day of hypericum for chronic depression. She had discontinued taking Paxil 10 days prior to hypericum and experienced no ill effects at that time. However, she added 20 mg of paroxetine to her regimen of hypericum to improve her sleep. She presented with lethargy, nausea, and weakness, but vital signs and mental status were normal. Following discontinuation of medications, she returned to normal status the next day. 

Given the wide availability and usage of hypericum, manic reactions such as the ones described appear to be uncommon. As expected, concomittant use of hypericum with pharmaceutical antidepressant medication appears to be contraindicated. Although some antidepressant medications can be given in combination, this must be done with caution and with dosage considerations to account for additive or synergistic effects. 

Sexual function One of the potential benefits of hypericum is the apparent reduced or lack of adverse effects upon sexual function, compared to pharmaceutical antidepressants. The SSRIs are particularly notorious for inhibition of sexual function, whereas antidepressants with dopaminergic actions (e.g., bupropion) do not, and may actually enhance sexual function (Rosen et al. 1999 Piazza et al. 1997). Anecdotal reports and the fact that there are no clinical reports of sexual dysfunction with hypericum is encouraging, but it remains to be tested empirically. 

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. 

Hypericum not only has a long tradition of use as an antidepressant, but also a considerable amount of scientific research to support it. More research is needed, but it certainly works better than placebo and may be as efficacious as pharmaceutical antidepressants. The mechanism of this effect is not certain although monoamine reuptake mechanisms are most likely involved. Various other mechanisms may contribute additive or synergistic effects. 

Butterweck V, Wall A, Lieflander-Wulf U, Winterhoff H, Nahrstedt A. (1997). Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity. Pharmacopsychiatry. 30(suppl. 2) 117-24. 

Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Muller WE. (1998a). Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci. 63(6) 499-510. 

Chatterjee SS, Noldner M, Koch E, Erdelmeier C. (1998b). Antidepressant activity of hypericum perforatum and hyperforin the neglected possibility. Pharmacopsychiatry. 31(suppl 1) 7-15. 

Ernst E, Rand JI, Barnes J, Stevinson C. (1998). Adverse effects profile of the herbal antidepressant St. John s wort (Hypericum perforatum L.). EurJ Clin Pharmacol. 54(8) 589-94. 

Hansgen KD, Vesper J, Ploch M. (1994). Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol. 7(suppl 1) S15-8. 

Muldner H, Zollner M. (1984). Antidepressive wirkung eines auf dem Wirkstoffkomplex Hypericin starndardisierten Hypericum-Extraktes. Arneimittelforschung. 34 918-20. 

Ozturk Y. (1997). Testing the antidepressant effects of Hypericum species on animal models. Pharmacopsychiatry. 30(suppl 2) 125-28. 

Several natural products have been evaluated in rodent models of nicotine withdrawal. An extract of Hypericum perforatum (St. John s Wort, a putative antidepressant, and inhibitor of serotonin reuptake) reversed somatically expressed withdrawal behaviors and locomotor depression in spontaneous withdrawal (Catania et al. 2003). A benzoflavone compound isolated from Passiflora incarnata, interfered with the induction of physical dependence. Coadministration with chronic nicotine prevented various subsequent indicators of withdrawal syndrome in the mouse, including jumping, locomotor inactivity, immobility in the swim test and naloxone-precipitated escape jumping (Dhawan et al. 2002). 

Herbal antidepressants - St John s Wort (Hypericum officinalis)... 

Flavonoids in the diet have been widely promoted as important antioxidant contributors. Their neuroprotective properties, because of this effect, have been demonstrated by several workers. However, they have also been demonstrated to have MAOI activity and this has been proposed as part of the explanation of the use of the common herb, St Johns Wort, Hypericum perforatum L., as an antidepressant. This dual role has now been proposed for a variety of flavonoids, such as kaempferol (22) from the leaves of Ginkgo biloba L., a widely used herbal product which has been suggested as a preventative agent against neurodegeneration. Quercetin (23), similarly, has also shown to inhibit MAO-B " and reverse the effects of induced catalepsy, which mimics the bradykinesia associated with PD. Tangeretin (24) also inhibits MAO-B and crosses the blood brain barrier in a rat model. 

Hypericum perforatum, more commonly known as Hypericum or St. John s wort, is used widely because of the perception that it is a safer, natural antidepressant. In Germany, Hypericum is used more extensively than conventional antidepressants for treating depression. Because St. John s wort has been attracting increasing media attention worldwide, consumption of this herb is likely to become more prevalent. 

As with prescription antidepressants, there is a 2- or 3-week lag in onset of action. If side effects are marked, or if at 6 to 8 weeks Hypericum is deemed to be ineffective, the patient can be weaned off and another treatment considered. Unfortunately, there are no data about washout periods following discontinuation of St. John s wort. A conservative approach is to wait 2 weeks after ceasing St. John s wort before commencing another agent. 

Greenblatt DJ, von Moltke LL, Harmatz JS, et al Human cytochromes and some newer antidepressants kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 19 23S-35S, 1999 Karliova M, Treichel U, Malago M, et al Interaction of Hypericum perforatum (St. John s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33 853-855, 2000 Michalets EL Update clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 18 84-112, 1998... 

The natural antidepressant hypericum perforatum is reported to have only few effects on cognitive and psychomotor performance in healthy volunteers after single doses of 900 and 1800mg only one test (DSST) within a large battery was significantly affected (Timoshanko et al., 2001). The effects of single doses of lithium on healthy volunteers are small. This also holds true when the substance is given over a period of several weeks. 

Sharpley, A.L., McGavm, C.L., Whale, R., et al. Antidepressant-like effect of hypericum perforatum (St John s wort) on the sleep polygram. Psvchophannacologv 139, 286-287, 1998. 

This herbal product has the most data available to support its usefulness as an antidepressant. Nevertheless, only minimal information is available about its pharmacology and its relative risk-benefit ratio. At least seven different biologically active chemicals have been isolated from crude extracts of hypericum. Several are ubiquitous in the plant kingdom. The exceptions are hypericin and pseudohypericin, which have been assumed to be responsible for any antidepressant activity of this product. Nevertheless, there is the potential for one or more of these seven compounds and their metabolites to mediate desired or undesired effects, particularly when used in combination with other medications (i.e., herb-drug interactions). 

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