depression

General practitioners and St. John's Wort: A question of regulation or knowledge?: Complement Ther Med. 2007 Jun; 15(2): 142-8. Authors: McGarry H, Pirotta M, Hegarty K, Gunn J

BACKGROUND: St. John's Wort (SJW), also known as Hypericum perforatum, is a herbal remedy available over-the-counter. There is evidence that it can treat mild to moderate depression but has potential side effects and important drug interactions. OBJECTIVE: To determine general practitioners' (GPs') knowledge and recommendation of SJW for mild to moderate depression within a climate of widespread community use of complementary therapies and debate about regulation. DESIGN AND SETTING: Postal survey of a random sample of 350 Australian GPs. RESULTS: Forty-eight percent responded. One-third (31%) reported recommending SJW to patients with mild to moderate depression. Of these, only one-third (32%) reported specific dosage instructions. Respondents' knowledge of side effects and interactions was much less than for selective serotonin reuptake inhibitor antidepressants. CONCLUSIONS: Australian GPs know less about safety of SJW than antidepressants and do not widely recommend it to patients. Despite this, many patients use SJW, probably in combination with other pharmaceuticals. Effective dissemination of further research into effectiveness and risk profiles of complementary therapies is needed to inform health professionals, regulatory bodies and consumers.

Update and critique of natural remedies as antidepressant treatments.: Psychiatr Clin North Am. 2007 Mar;30(1):51-68 Authors: Mischoulon D

Natural medications such as St. John's Wort, SAMe, and omega-3 fatty acids eventually may prove to be valuable additions to the psychiatrist's pharmacologic armamentarium, both as monotherapy and as adjunctive therapy for mood disorders. Current research data are compelling, from a standpoint of both efficacy and safety, but before clinicians can recommend these as first-line treatments, more well-designed controlled studies in large patient populations are needed. During the past decade, the National Institutes of Health, the National Institute for Mental Health, and the National Center for Complementary and Alternative Medicine have widened their support for research on the efficacy and safety of alternative treatments, and increasing numbers of academic institutions are undertaking large-scale, multicenter studies on the natural medications reviewed here, as well as others. These studies should help answer some of the yet-unsettled questions about natural medications. Psychiatrists who are considering recommending natural antidepressants to their patients should emphasize that these treatments are relatively unproven and that it remains to be seen whether they would be appropriate or preferable to the conventional psychotropic agents. in the absence of more conclusive data, the best candidates for alternative treatments may be patients for whom a delay in adequate treatment would not be devastating(eg, the mildly symptomatic patient who has a strong interest in natural remedies). Other good candidates may include patients who have been unresponsive to conventional antidepressants or particularly intolerant of side effects; these patients, however, often are the most difficult to treat, and alternative agents seem best suited for the mildly ill. Care should be taken with patients who are taking multiple medications, in view of adverse drug-drug interactions that have emerged with increased use of alternative treatments. Finally, as with all psychotropic agents, natural medications should be used preferably under the supervision of a physician.

A mechanistic study on altered pharmacokinetics of irinotecan by St. John's wort.: Curr Drug Metab. 2007 Feb;8(2):157-71 Authors: Hu ZP, Yang XX, Chen X, Cao J, Chan E, Duan W, Huang M, Yu XQ, Wen JY, Zhou SF

Irinotecan (CPT-11) is an important anticancer drug in management of advanced colon cancer. A marked protective effect on CPT-11-induced blood and gastrointestinal toxicity is obtained by combination of St. John's wort (SJW) in recent clinical and rat studies. However, the mechanism is unclear. This study aimed to explore the effects of SJW on the pharmacokinetics of CPT-11 and its major metabolites (SN-38 and SN-38 glucuronide) in rats and the underlying mechanisms using several in vitro models. Short-term (3 days) and long-term (14 days) pretreatment with SJW were conducted in rats to examine the effects of co-administered SJW on the plasma pharmacokinetics of CPT-11, SN-38 and SN-38 glucuronide. Rat liver microsomes and a rat hepatoma cell line, H4-II-E cells, were utilized to study the effects of aqueous and ethanolic extracts (AE and EE) and major active components (hyperforin, hypericin and quercetin) of SJW on CPT-11 and SN-38 metabolism and intracellular accumulation. Co-administered SJW for consecutive 14 days significantly decreased the initial plasma concentration (C0) of CPT-11, the area under the concentration-time curve (AUC(0-10hr)) and maximum plasma concentration (Cmax) of SN-38. The ethanolic extracts (EE) of SJW at 5 microg/ml significantly decreased SN-38 glucuronidation by 45% (P < 0.05) in rat hepatic microsomes. Pre-incubation of aqueous SJW extracts (AE) at 10 microg/ml, SJW EE at 5 microg/ml, and quercetin at 10 microM significantly increased the glucuronidation of SN-38 in H4-II-E cells. A 2-hr pre-incubation of quercetin (100 microM) significantly increased the intracellular accumulation of CPT-11 (P < 0.05). However, pre-incubation of hypericin (20 nM and 200 nM) and hyperforin (1 microM) significantly decreased the intracellular accumulation of CPT-11. In addition, pre-incubation of hypericin, SJW EE and quercetin significantly increased the intracellular accumulation of SN-38. Aqueous and ethanolic SJW extracts and its major active components did not alter the plasma protein binding of CPT-11 and SN-38. These results indicated that the aqueous and ethanolic extracts of SJW and its major active components could markedly alter glucuronidation of SN-38 and intracellular accumulation of CPT-11 and SN-38, which probably provides partial explanation for the altered plasma pharmacokinetics of CPT-11 and SN-38 and the antagonizing effects on the toxicities of CPT-11. Further studies are needed to explore the role of both pharmacokinetic and pharmacodynamic components in the protective effect of SJW against the toxicities of CPT-11.

Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice.: Phytother Res. 2007 Jan;21(1):37-43 Authors: Perfumi M, Mattioli L

Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time.

The extent of induction of CYP3A by St. John's wort varies among products and is linked to hyperforin dose.: Eur J Clin Pharmacol. 2006 Jan;62(1):29-36 Authors: Mueller SC, Majcher-Peszynska J, Uehleke B, Klammt S, Mundkowski RG, Miekisch W, Sievers H, Bauer S, Frank B, Kundt G, Drewelow B

OBJECTIVE: Induction of CYP3A by St. John's wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content. METHODS: Forty-two male, healthy volunteers were randomized into six parallel SJW medication groups with varying composition especially with regard to HYF content. Midazolam plasma concentration profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication. RESULTS: All SJW preparations tested resulted in a decrease in midazolam AUC, although the extent of the effect differed. The extract LI 160 (HYF 41 mg/day) decreased midazolam AUC0-12h by 79.4% (95% CI -88.6; -70.1), which was significantly greater than the effect by any other medication (p<0.05). SJW powder tablets 2.7 g/day (HYF 12 mg/day) resulted in a midazolam AUC0-12h decrease of 47.9% (95% CI -59.7;-36.2), while 2.7 g/day SJW powder tablets that were almost devoid of HYF (0.13 mg/day) reduced midazolam AUC0-12h by only 21.1% (95% CI -33.9; -8.3). Considering all six SJW medications tested, the extent of midazolam AUC decrease correlated significantly with increasing HYF dose (r=-0.765, p<0.001), but not with hypericin dose (r=-0.067; p=0.673). CONCLUSION: The extent of induction of CYP3A varies among St. John's wort products and depends on hyperforin dose.

[Effects of lavender aromatherapy on insomnia and depression in women college students]: [Effects of lavender aromatherapy on insomnia and depression in women college students] Taehan Kanho Hakhoe Chi. 2006 Feb;36(1):136-43 Authors: Lee IS, Lee GJ

PURPOSE: The purpose of this study was to explore the effects of the lavender fragrance on sleep and depression in women college students. METHOD: Forty-two women college students who complained of insomnia were studied during a four-week protocol(control treatment week, 60% lavender fragrance treatment week, washout week, 100% lavender fragrance treatment week). All subjects were in the department of nursing in "K" college and the study was a single blind repeated measurements experiment. For the duration of the study, weekly evaluations of sleep, patterns of sleep disturbance, severity of insomnia scale, self satisfaction with sleep, and severity of depression were performed. RESULT: Among sleep variables, length of time taken to fall asleep, severity of insomnia, and self satisfaction with sleep were improved for the 60%(p=.000, p=.000, p=.000) and 100%(p=.000, p=.000, p=.000) week while the severity of depression was improved only for the 100%(p=.002) week. CONCLUSION: According to the study results, it can be concluded that the lavender fragrance had a beneficial effect on insomnia and depression in women college students. Repeated studies are needed to confirm effective proportions of lavender oil and carrier oil for insomnia and depression.

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.: Phytother Res. 2005 Oct;19(10):901-6 Authors: Donovan JL, DeVane CL, Lewis JG, Wang JS, Ruan Y, Chavin KD, Markowitz JS

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

Functional dyspepsia pathogenesis and therapeutic options--implications for management.: Dig Liver Dis. 2005 Aug;37(8):547-58 Authors: Smith ML

Functional dyspepsia is far more common than dyspepsia due to organic disease, both in the community and general practice. Proposed aetiopathogenic factors include gastric acid, Helicobacter pylori infection, delayed emptying, hypersensitivity or impaired accommodation of the stomach, dysfunction of the duodenum or brain-gut axis, psychosocial morbidity and post-infective mucosal damage. More effective therapy will depend on the development of drugs targeted at these putative pathophysiological mechanisms. On current evidence tricyclic antidepressants appear to be more effective than either acid suppressants or H. pylori eradication.

Can St John's wort (hypericin) ingestion enhance the erythemal response during high-dose ultraviolet A1 therapy? - Br J Dermatol. 2005 Dec;153(6):1187-1191  Authors: Beattie PE, Dawe RS, Traynor NJ, Woods JA, Ferguson J, Ibbotson SH

Summary Background St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy. Objectives To assess the phototoxicity risk of SJW ingestion. Methods Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70-77 mW cm(-2)) on the photoprotected lower back skin at eight 1.5-cm(2) test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 microg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter. Results The median MED and D(0.025), an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm(-2), range 10-56) than at baseline (median 20 J cm(-2), range 14-56) (P = 0.047). Similarly, the median D(0.025) at 8 h postirradiation was lower after SJW (median 22.0 J cm(-2), range 15.2-53.9) than at baseline (median 33.7 J cm(-2), range 22.9-136.0) (P = 0.014). The MED and D(0.025) were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose-response curve was not increased after SJW ingestion. Conclusions These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.