alternatives treatments for depression 2

light and st johns wort

The universe is full of magical things patiently waiting for our wits to grow sharper. Eden Phillpotts
This is the second in a series of three articles by James Hawkins on alternative treatments to drugs and talking therapies for depression. The first article focused on exercise and wake therapy. This article explores the value of light and St Johns wort. The third will look at food and supplements, meditation, acupuncture, bibliotherapy, and the internet.

about the author:

I am a medical doctor, Chinese-trained acupuncturist and accredited cognitive therapist. I also chair the clinical advisory group for Depression Alliance Scotland, the countrys main consumerled charity for depression sufferers. In 1983 I was one of the initial group of doctors who set up the BHMA. Currently I work through Good Medicine a small Edinburgh-based charity that focuses on helping people with psychological difficulties. Good Medicine tries to use therapies (conventional, complementary and self-help) with better research support before, if necessary, adding in methods that are currently less evidence-based. Good Medicine is also clear that knowledge evolves but the heart of medicine remains constant in the care and sensitivity with which it is practised.

summary:
When all depressive subtypes are included, more than 1 in 3 of us is likely to have qualified for a depression diagnosis by our mid 30s [1]. All these depression subtypes are associated with significant suffering as well as disturbance in work and social functioning. This is true too for the even commoner subthreshold disorders [2, 3]. This article explores the value of light therapies and St Johns wort for these widespread difficulties.

light:
A major paper entitled The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence was published in the American Journal of Psychiatry in April 2005 [4]. This recent study concluded analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. A Cochrane Collaboration systematic review published the year before [5] just looked at the value of bright light treatment for nonseasonal depression and concluded For patients suffering from non-seasonal depression, bright light therapy offers modest though promising antidepressive efficacy, especially when administered during the first week of treatment, in the morning, and as an adjunctive treatment to sleep deprivation responders. Mental health professionals are surprisingly unaware of these findings as too are many general practitioners and other therapists. Dr Norman Rosenthal, who has probably done more than anyone to advance the use of light therapy for depression, commented on the 2005 review [6] saying It is certainly an area in which clinicians need more education when it comes to pharmaceutical treatments of depression and other conditions, physicians are constantly being educated by pharmaceutical representatives and at industry-sponsored dinners and symposia. But when there is no money to be made, no such opportunities for education arise, and public agencies would do well to step in and fill the vacuum. Rosenthal first described the value of light in the treatment of depression in a paper published over 20 years ago [7]. The recent American Journal of Psychiatry meta-analysis initially identified 173 papers of potential relevance published up to July 2003 most were excluded from

their subsequent analysis as they did not meet the systematic reviews strict inclusion criteria. 20 randomized controlled trials were finally studied in detail. 8 of these involved bright light and 5 dawn simulation for seasonal affective disorder (SAD). 3 studies involved bright light for nonseasonal depression. A further 5 studies looked at the potential value of bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression. This last application of bright light as a support for antidepressants was the only group of studies that the metaanalysis did not conclude showed effectiveness. A whole series of further papers have been published since 2003, including some new evidence suggesting light might, after all, be of value in boosting the effects of antidepressants for nonseasonal depression [8]. Increasing our exposure to light tends to improve our mood. This is true for many of us, and especially so for a subgroup who suffer from subsyndromal or full syndrome seasonal affective disorder (SAD). Interestingly it seems that most types of depression show some worsening in the winter [9, 10], so what distinguishes SAD from other depression forms may be more a quantitative rather than a qualitative difference in response to seasonal change. For example, a group of Italian researchers noted that bipolar disorder patients exposed to morning sunlight in East-facing rooms had an average 3.7 days shorter hospital stay than bipolar patients in West-facing rooms [11]. In fact surveys in the general population suggest that, for women particularly, it is normal to suffer quite considerable worsening of general symptoms in the winter [12]. Thus seasonal variation seems common for anxiety, irritability and hostility [13]. Panic disorder, as well, frequently shows seasonal alterations in severity [14] as too may temporomandibular joint syndrome and myofascial facial pain [15, 16], eating disorders [17], premenstrual syndrome [18, 19] and fatigue [20]. US surgeons have even found that surgery patients staying in rooms on the sunnier side of their hospital reported less stress, less pain and had 21% lower medication costs than patients on the less sunny side of the building [21]. No doubt, in the future, the severity of a number of other disorders will be shown to be sensitive to the quantity of available light. For those who do notice that they tend to feel worse in winter, it makes good sense to explore whether getting more light would be helpful. Even healthy people suffering from no obvious disorder may find their energy is boosted by increasing their light exposure [22]. Bright light therapy has traditionally been used for seasonal affective disorder (SAD), a form of depression that develops in the autumn and remits in the spring. SAD typically also involves increased fatigue and sleep, increased appetite and weight, and decreased social activity. It has been estimated that approximately 5% of the UK population suffer from SAD [23-25]. Probably at least twice as many people suffer from milder subsyndromal SAD [26]. It has been argued that SAD is a sort of attenuated hibernation response that had evolutionary advantage particularly for women. The winter depression and associated springtime activation made it more likely that such women would become pregnant in the summer and give birth the next spring thus giving their babies a higher chance of survival [27]. Whatever the true explanation, increasing our exposure to sunlight is an obvious way to improve symptoms in SAD and other light-sensitive disorders. This can be achieved by encouraging sufferers to get out into daylight more often this is usefully combined with physical exercise. For those who can afford it, a winter holiday to somewhere with good sunlight can also be a welcome boost. More extremely, some people will move house to a latitude less far from the equator. In this latter case, it is worth knowing that there are also seasonal disorders of too much heat characterised by symptoms like poor sleep, loss of appetite and fatigue. In fact it may be that, in worldwide terms, summer seasonal disorders produce even more difficulties than winter seasonal disorders [28]. Most research however has concentrated on ways of increasing light exposure by artificial means. Bright light boxes and dawn simulation lights (light alarms) are the two ways of doing this that have a good evidence base. Portable light visors have also been tried, but current visor models may act more by a non-specific placebo effect than by the effects of light itself [29-31]. As is so often the case in medicine generally, at times the placebo effect makes interpretation of studies on light therapy more complicated to interpret. For bright light boxes, Golden et al in their meta-analysis [4] only included studies that provided a minimum of 4 days of at least 3,000 lux hours (e.g. 1,500 lux for 2 hours or 3,000 lux for 1 hour). A lux is a widely used unit of illumination intensity. There are many useful websites providing good advice on how to use light

boxes. See for example the British Seasonal Affective Disorder Association (SADA) www.sada.org.uk , the Society for Light Treatment & Biological Rhythms (SLTBR) www.sltbr.org , Dr Lams site at the University of British Columbia www.psychiatry.ubc.ca/mood/sad , Dr Kripkes site www.dankripke.org , and the fine Canadian Consensus Guidelines www.psychdirect.com/depression/d-treatmentguidelinesSAD.htm . The Canadian Guidelines, published in 1999, give good research-based advice on how best to use bright light therapy. Key points they make include:

The fluorescent light box, with light intensities of greater than 2,500 lux, is the preferred
device for light therapy.

Some patients may respond to other light devices, such as head mounted units and dawn

simulators. The starting dose for light therapy using a fluorescent light box is l0,000 lux for 30 minutes per day. Alternatively, light boxes emitting 2,500 lux require two hours of exposure per day. Correct positioning is important (e.g. sitting close enough to the light box) to obtain the correct illumination. Light boxes should use white, fluorescent light with the ultraviolet wavelengths filtered out. Light therapy should be started in the early morning, upon awakening, to maximize treatment response, but exposure at other times of the day may be helpful for some patients. Response to light therapy often occurs within one week, but some patients require two to four weeks to show a response. Patients can be encouraged to become active participants in establishing an optimal light protocol. Common side effects of light therapy include headache, eyestrain, nausea and agitation, but these effects are generally mild and transient, or resolve with reducing the dose of light. There are no absolute contraindictions to light therapy and no evidence that light therapy is associated with ocular or retinal damage. Patients with ocular risk factors should have a baseline ophthalmologic consultation prior to starting light therapy, and periodic monitoring. Risk factors for retinal toxicity to bright light exposure are: pre-existing retinal or eye disease (e.g., retinal detachments, retinitis pigmentosa, glaucoma); systemic illnesses that affect the retina (e.g., diabetes mellitus); previous cataract surgery and lens removal; older age, because of greater risk of age-related degeneration; and taking medications that have photosensitizing effects in humans e.g. lithium, phenothiazines such as thioridazine (antipsychotics, antiemetics), chloroquine (antimalarial), hematoporphyrins (used in photodynamic therapy for cancer), 8methoxypsoralens (used in ultraviolet treatment for psoriasis), melatonin, and hypericum (St. Johns Wort).

It is sensible to also add a caution about the possible risk of light-induced mania. Probably all treatments for depression occasionally cause a switch from depression to mania in vulnerable individuals. Especially if someone has any history of mania or hypomania, they should use light therapy very cautiously and consider possible pre-treatment with a mood stabilizing agent if they are not already taking such medication. Fascinatingly dark therapy staying in a darkened room away from all light seems to have some value in the treatment of mania [32]. For further detailed information about diagnosis, assessment, prevalence, possible use of standard antidepressants and other details, the Canadian guidelines site is well worth visiting (see address given above). Dr Lams University of British Columbia site (see above) is also hugely useful with a free 45 page health professional download that contains handouts and questionnaires that are formatted to be easily printed. Also of considerable interest is the freely downloadable 35 page PDF from Dr Kripkes site. If you decide you want to explore the use of light further, there are numerous manufacturers of light boxes and light alarms. Unfortunately these devices are not usually available on the NHS and have to be bought from specialist retailers. Typically light boxes can be bought free of VAT and prices range from approximately 100 to 300. The more expensive units usually provide more intense light allowing shorter duration treatments and the convenience of not having to sit so close to the light box. Light alarms are cheaper, ranging from about 60 to 100. Besides the price differential, light alarms

do not take time out of your day as the treatment occurs while you are waking up. Alarms are also very unlikely to interact with photosensitizing medications like St Johns Wort and so are safer if you are taking such substances. However there is less research on light alarms than light boxes so, even if a light alarm fails to help, it is well worth trying a light box as well. Since the two forms of therapy probably act by different mechanisms, it may be that their benefits are additive. I know of no research that has tested this possibility so far. Several companies offer a home trial or hire scheme and the British Seasonal Affective Disorder Association (SADA) also has a number of boxes for short-term hire. An internet search will bring up a number of suppliers. In alphabetical order, examples include: National Light Hire Company - www.sad-lighthire.co.uk/index.html - free phone 0800 074 1105. Outside In - www.outsidein.co.uk/index.htm - phone 01954 780500. The S.A.D. Lightbox Company - www.sad.uk.com/home.php - phone 01494 484852.

St Johns Wort & other herbs:

This section of the article will almost entirely be devoted to St Johns Wort. This is because there is so little good research supporting the value of other herbs in the treatment of depression. There is some work, for example on crocus [33, 34], but it is very limited and there currently seems no good evidence-based reason to recommend any other herbal preparation besides St Johns Wort for depression treatment. In contrast, the literature on St Johns Wort is confusing, not because of lack, but because of its quantity and its mixed conclusions. The most recent major Cochrane review of St Johns Worts effectiveness in treating depression[35] was updated in February 2005. It covers 37 rigorously selected randomized controlled trials - 26 include comparisons with placebo and 14 include comparisons with standard synthetic antidepressants. There were half a dozen earlier systematic reviews published between 1995 and 2000 [35]. In general these reviews painted a rather positive picture of St Johns Wort suggesting it was more effective than placebo, as effective as synthetic antidepressants (at least for mild to moderate depression), and better tolerated than synthetic antidepressants in the treatment of adult depression. A recent systematic review of large-scale observational studies also suggests worthwhile benefit and few side effects from St Johns Wort treatment of mild to moderate depressive disorder [36]. The National Institute for Clinical Excellence (NICE) guideline on depression treatment see www.nice.org.uk was published at the end of 2004 based on literature searches that were updated over most of 2003. This guideline included a systematic review of St Johns Wort research and recommendations about its use that are discussed further below. The Cochrane review is slightly more recent than the NICE guideline as it covers research published up till April/May of 2004. Since then several other interesting studies have come out [37-40] including a further systematic review [41]. The Cochrane review acknowledged several major criticisms of St Johns Worts value in more recently published research both suggesting that, with some forms of depression, it might be no more effective than placebo [42-44] and that its interactions with other widely used standard medications could be a very real source of harm [45-47]. However, when all good research results were combined, the review concluded that overall St Johns Wort appears as effective as standard antidepressants and is associated with lower drop out rates due to adverse effects. In a similar vein, the NICE guideline found very little difference between the effectiveness of St Johns Wort and standard antidepressants. In fact the NICE review concluded (p.230) that In moderate depression there is some evidence suggesting that there is a clinically significant difference favouring St Johns Wort over antidepressants on achieving the likelihood of a 50% reduction in depression symptoms ... , and even the NICE reviews proposition that standard antidepressants may sometimes be more effective than St Johns Wort for severe depression is highly qualified as it makes this statement in relation to low dose (not standard or high dose) tricyclics (not SSRIs) an observation which is largely irrelevant to standard medical treatment of depression. The 2004 NICE guideline Depression: management of depression in primary and secondary care is probably the key source of evidence-based advice on how UK doctors should currently treat depression. The guidelines comments on St Johns Wort are challenging and to some extent puzzling. In their clinical summary (p. 231) the herb is acknowledged to be ... more

effective than placebo on achieving response in both moderate and severe depression ... . Further commendation comes with the conclusion that There appears to be no difference between St Johns Wort and other antidepressants, other than in moderate depression where it is better at achieving response ... and the encouraging finding that ... St Johns Wort appears as acceptable as placebo, and more acceptable than antidepressants, particularly TCAs, with fewer people leaving treatment early due to side-effects and reporting adverse events. One might understandably conclude that St Johns Wort is now going to be recommended over synthetic antidepressants as the preferred first line treatment for depression. Far from it the guideline (p. 234) states ... healthcare professionals should not prescribe or advise its use by patients because of uncertainty about appropriate doses, variation in the nature of preparations and potential serious interactions with other drugs ... . At least they have the honesty to acknowledge this recommendation as only level C just supported by level IV evidence the lowest evidence grade cited by the guideline (p.46). Level IV evidence is based on ... expert committee reports or opinions and/or clinical experiences of respected authorities. In other words there is no level I evidence (randomized controlled trials or meta-analyses), level II evidence (well conducted non-randomized trials), or even level III evidence (well designed descriptive work such as comparative, correlation and case studies) to back up the guidelines recommendations on St Johns Wort. St Johns Wort is a newcomer on the block as far as the medical establishment is concerned. To be blunt, doctors have been wined and dined by the drug industry for far too long. We know from level I evidence (p.179 of the guideline) that Most studies of the effects of drugs are sponsored by the drug industry, and these have been shown to be more than 4 times as likely to demonstrate positive effects of the sponsors drug as independent studies.[48] There has been a blizzard of further solid reports and research studies showing that bias is a huge problem in the drug literature [49-53]. Level I evidence meta-analysis even throws serious doubts on just how effective synthetic antidepressants really are [54]. If the medical establishment is going to make an evidence-based statement that keeps the outsider St Johns Wort from joining the party, it seems to me that we need better data for taking that recommendation particularly seriously than level IV opinions and/or clinical experiences of respected authorities. As has frequently been noted The plural of anecdote is not data. To give the NICE guideline its due, it notes (p.8) that Guidelines are not a substitute for professional knowledge and clinical judgement. So when might one consider using St Johns Wort for depression? I can see several possible reasons why an informed practitioner or depression-sufferer might well think seriously about this option. These include: Negative attitudes to synthetic antidepressants. A large scale survey [55] of general public attitudes to depression in the UK published in 1996 found that 85% believed counselling to be effective but were against antidepressants with 78% regarding antidepressants as addictive. More recent publicity on the increased suicidal thoughts many people may face early in treatment, problems with side-effects during treatment, and difficulties when trying to come off these medications, combines with the stigma many people feel taking these drugs to produce very understandable problems with acceptance and compliance. This may well mean that many depression-sufferers who would benefit from treatment, are not prepared to accept the offer of a synthetic antidepressant. Clinical experience suggests that quite a high proportion of these people would be prepared to try St Johns Wort. It would be fascinating to check this impression in a clinical trial. A preferable side-effect profile. Meta-analysis has repeatedly shown that St Johns Wort is better tolerated than synthetic antidepressants. Besides the probems already mentioned, synthetic antidepressants are often plagued by their aggravation of sexual difficulties [56, 57] weight gain [58], nausea, diarrhoea, headache and other problematic effects including, of course, the danger of fatal overdose [59]. The most commonly reported side-effects with St Johns Wort are gastrointestinal symptoms such as nausea, dermatological symptoms such as itching and increased light sensitivity, and occasionally fatigue, sleep disorders, and headache. It is well worth noting though that, in randomized controlled trials, St Johns Wort only produces side-effect rates that are similar to those produced by inactive placebos [45]. Increased effectiveness with certain types of depression. Much more research is needed here, but there is preliminary data suggesting St Johns Wort may be a good treatment choice with atypical symptoms such as increased appetite and increased sleep [39], where there are

multiple unexplained physical (somatoform) symptoms [40], in juvenile depression [60], and in agitated depression [61]. Key issues to note if someone is taking or considering taking St Johns Wort are the potential for drug (and light) interactions, the variability of different types of St Johns Wort, and the obvious need to review treatment if, after about four weeks, there is inadequate treatment response. Drug interactions are common with many medications. For example the NICE guideline notes (p.199) that the SSRIs Fluvoxamine, fluoxetine and paroxetine are potent inhibitors of various hepatic cytochrome metabolising enzymes precipitating many significant drug interactions. In this kind of situation care, but not a blanket veto on use, is needed. To quote a recent authoritative systematic review of adverse effects due to St Johns Wort [45] A wide range of drug interactions has been described in the recent past [46], but the clinical relevance of these interactions is not clear, as many of these interactions as actual side effects in patients have not been observed or reported. The lowering of plasma cyclosporine concentration in transplant patients is obviously of great importance ... Hypericum extracts should also not be used in HIV-infected patients receiving antiretroviral treatment. In patients receiving anticoagulants of the coumarin type, the use of hypericum is only acceptable if coagulation parameters are regularly monitored. Simultaneous use of hypericum extracts and other antidepressants, particularly SSRIs, is inadequate and can be harmful. The question whether hypericum extracts interact with oral contraceptives is of major relevance but has been difficult to answer up to now. A recent randomized trial [62] in a limited number of healthy females taking low-dose oral contraceptives found no evidence of ovulation in subjects taking a hypericum extract, but intracyclic bleeding episodes increased. Patients should be informed that an interaction cannot be ruled out with certainty. Finally hypericum extracts should be avoided in patients with a known allergy or hypersensitivity to such products. The March 2005 edition of the British National Formulary[63] (BNF) gives a longer list of possible problematic interactions between St Johns Wort and other medications, including some antiepileptics, digoxin, simvastatin, theophylline, and other drugs. Generally what happens is that St Johns Wort lowers blood levels of these agents. It is therefore important, if you are considering taking St Johns Wort with any other medication, that you check on the safety of the combination. Strength of interaction is likely also to vary with the brand of St Johns Wort [64]. It is well worth noting though that the list of cautions for St Johns Wort is considerably shorter than the list of possible drug interactions given by the BNF for SSRI antidepressants, for tricyclic antidepressants or even for antihistamines. The sensible and very informed Knuppel and Linde review went on to report research showing that available St Johns Wort preparations can vary considerably in quality and even batch to batch composition [65-67]. The authors suggest that ideally one should use products that have been tested in clinical trials the most widely researched is the Kira brand produced by Jarsin and quite easily available in the UK. They go on to suggest that one should avoid products that do not give important content information such as the amount of total extract, the extraction fluid, and the raw material to extract ratio. One economic option would be for an individual to start with the relatively expensive Kira brand and, if there is an adequate response, then later see whether a reputable but cheaper alternative product is as effective. I will leave the final coment on St Johns Wort to Klaus Linde whose meta-analysis[35] has been so helpful in clarifying the value of this herb: In conclusion, the available evidence suggests that hypericum extracts are well tolerated and safe if taken under the control of a physician who is aware of potential risks in specific circumstances. Self-medication might be acceptable in patients who have very mild depressive symptoms and who are not taking any other medication.[45]

conclusion:
This article began by emphasising how very common depression is. The potential values of light and St Johns Wort were then described in some detail. Both interventions have much to recommend them and are well worth considering as alternatives or complements to more widely used therapies.

a note for depression sufferers:

Information in this article is not a substitute for seeking expert help. If you feel you may be depressed, please see your family doctor or other qualified health professional. You can always show them this article and discuss these treatments with them.
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