Herbal Medicines and Other Natural Supplements for Drug and Alcohol Abuse and Withdrawal: A Concise Review

This is the fourth installment in a series of posts on non-pharmacologic approaches to alcohol and drug abuse. Previous posts reviewed the evidence for weak electrical current for reducing symptoms of opioid and alcohol withdrawal. This post is offered as a concise review of promising herbal and other natural product treatments of alcohol craving and withdrawal, narcotic withdrawal and benzodiazepine withdrawal.

Traditionally used herbal medicines may reduce alcohol craving, lessen alcohol consumption and reduce symptoms of withdrawal

Three herbs are used in Chinese medicine to diminish alcohol craving, lessen alcohol absorption through the gut, or reduce symptoms of withdrawal. Kudzu (Radix puerariae) has been used as a treatment of alcohol abuse and dependence in Chinese medicine for almost 2000 years. Animal studies suggest that Kudzu extract significantly reduces alcohol craving (Keung 1993). A recent placebo-controlled human study found that individuals who had the opportunity to binge drink significantly reduced their drinking after taking 2gm of a standardized Kudzu extract 2 1/2 hours before starting to drink (Penetar 2015).

Salvia miltiorrhiza is a widely used herb in Chinese medicine that may reduce absorption of alcohol through the stomach. Animal studies suggest that S. miltiorrhiza reduces alcohol seeking behavior in rats genetically engineered to prefer alcohol. Blood alcohol levels were reduced by 60% in rats that had been pre-treated with S. miltiorrhiza. Aralia elata is a component of a compound Chinese herbal formula traditionally used to prevent or mitigate alcohol intoxication. Animal studies suggest that the herbal A. elata is a potent inhibitor of alcohol absorption (Yoshikawa 1996). Ibogaine is a naturally occurring alkaloid extracted from the root of an African shrub (Tabernanthe iboga). Preparations of the herb have been used as a stimulant in traditional African culture for centuries. Animal studies suggest that ibogaine and its primary metabolite, noribogaine, significantly reduce alcohol consumption in rats genetically engineered to prefer alcohol. Cannibis indica, an important Ayurvedic medicinal herb, may be an effective treatment for delirium tremens, a potentially fatal complication of acute alcohol withdrawal. Case reports from as early as the mid-19th century suggest that Cannibis indica provides rapid relief from symptoms of delirium tremens when administered orally in sequential doses over a 24-hour period (Godfrey 1996) (Please see full citation in references). The findings of an open trial suggest that Mentat, ™ a proprietary Ayurvedic compound herbal formula, may reduce the risk of relapse in abstinent alcoholics (Trivedi 1999). (Please see full citation in references)

Ashwagondha, Ginseng, and other natural products may reduce the severity of withdrawal from opiates, and reduce tolerance to cocaine, methamphetamine and morphine

Ashwagondha (Withania somnifera) is an important herb in traditional Ayurvedic medicine. Anecdotal reports and findings of animal studies suggest that Ashwagondha lessens the severity of withdrawal from morphine. Mice pre-treated with Ashwagondha for ten days did not develop tolerance to analgesic effects of morphine, suggesting that Ashwagondha may have similar beneficial effects in human heroin addicts (Ramarao et al, 1995; Kulkarni & Ninan, 1997). Ginseng (Panax ginseng) is widely used in both Chinese medicine and Western herbal medicine. Animal studies suggest that Ginseng may reduce tolerance and dependence associated with the long-term abuse of cocaine, methamphetamine or morphine. Repeated use of cocaine or methamphetamine results in chronically depleted dopamine. The mechanism of action responsible for reduced tolerance observed with Ginseng may involve inhibition of narcotic-induced depletion of dopamine in the brain.

Valerian extract and a proprietary Ayurvedic formula may reduce the severity of benzodiazepine withdrawal

Valerian (Valeriana officinalis) extract may lessen withdrawal symptoms and facilitate return to a normal sleep pattern following prolonged use of benzodiazepines such as clonazepam and lorazepam. The findings of animal studies show that Valerian in doses of 12mg per kilogram attenuates withdrawal symptoms in diazepam-dependent rats (Andreatini 1994). Mentat™, a proprietary Ayurvedic compound herbal formula, has been found to reverse effects of acute benzodiazepine withdrawal in dependent mice, and may provide similar benefits in humans (Kulkarni 1994; Kulkarni 1992).

Melatonin may help individuals discontinue benzodiazepines following prolonged use

Melatonin may facilitate discontinuation of benzodiazepines when there is dependence following chronic use. In a 12-week single-blind placebo-controlled study patients receiving controlled release melatonin 2mg/night were more likely to discontinue benzodiazepines compared to patients taking a placebo (Garfinkel 1999). Patients taking melatonin reported significantly greater improvements in subjective sleep quality compared to the placebo group. Most patients who continued to take controlled release melatonin at night remained off benzodiazepines six months after the end of the study. In view of these findings individuals who are attempting to taper and discontinue benzodiazepines following prolonged use for insomnia should be encouraged to take a nightly 2mg dose of controlled release melatonin. The above findings should be viewed in the context of a 2105 systematic review and meta-analysis that found no evidence that melatonin facilitated benzodiazepine discontinuation and inconsistent effects of melatonin on sleep quality (Wright 2015) .

Polyenylphosphatidylcholine (PCC) may reduce liver damage in chronic alcohol abuse

Polyenylphosphatidylcholine (PPC) is a natural product that is believed to reduce induction of liver enzymes associated with alcohol intake. Animal studies suggest that PPC reduces liver damage when taken before alcohol consumption (Lieber 1997; Aleynik 1999). HepatoPro ™ and other commercial products containing PPC are currently used before drinking in West European countries to protect the liver from damage.

Supplementation with fatty acids may reduce the severity of alcohol withdrawal, and improve mood and overall cognitive performance

Chronic alcohol use causes depletion of Omega-3 fatty acids and related molecules in nerve cell membranes, which in turn, may predispose alcoholics to depressed mood and other menta; health problems (Hibbeln 1995). In a small double-blind placebo-controlled trial supplementation with Omega-6 fatty acids in the form of Evening Primrose oil reduced the severity of withdrawal from alcohol, normalized liver enzymes, and significantly improved cognitive performance (Glen 1984). (Please see full citation in references).

Bottom line

Most studies on herbals and other natural supplements for reducing alcohol or drug use, reducing craving and managing withdrawal were small, conducted many years ago and have not been replicated by large placebo-controlled studies. Nevertheless, there is evidence that some herbal medicines widely used in Chinese medicine, Ayurveda (the system of medicine used in India) may significantly reduce craving and consumption of alcohol and may reduce the severity of alcohol withdrawal. A natural product called polyenylphosphatidylcholine may reduce liver damage in chronic alcohol abuse and fatty acid supplementation may reduce the severity of alcohol withdrawal while improving mood and overall cognitive performance. There is also evidence that the herbals ashwagondha, Ginseng, and select other natural products may reduce the severity of withdrawal from opiates, and reduce tolerance to cocaine, methamphetamine and morphine. Valerian extract and a proprietary Ayurvedic formula may reduce the severity of benzodiazepine withdrawal however, melatonin is probably not effective for facilitating discontinuation of benzodiazepines or improving sleep quality following chronic use.

If you are struggling with an alcohol or drug abuse problem it is prudent to consult with a mental health provider or an addiction specialist before considering any natural product supplement. 

Cranioelectrotherapy Stimulation for Alcohol and Cocaine Abuse and Withdrawal

Cranioelectrotherapy stimulation (CES) for alcohol and cocaine abuse and withdrawal

Numerous studies dating back to the 1970s have investigated the efficacy of weak electrical currents in the treatment a variety of mental health problems including anxiety disorders, depressed mood, insomnia and alcohol and drug abuse. Depending on the technique used, these therapies are described as cranioelectrotherapy stimulation (CES) transcranial electrical stimulation (TES). TES is widely used in Germany and other countries in the European Union for the management of alcohol and narcotic withdrawal. CES has been approved by the U.S. Food and Drug Administration (F.D.A.) as a treatment of chronic pain syndromes and anxiety and is widely used to treat both conditions. In my previous post I reviewed evidence for cranioelectrotherapy stimulation (CES) for reducing symptoms of opiate withdrawal. In this post I take a brief look at studies on CES for treating symptoms of alcohol withdrawal.

Review of research findings

In a 7-year prospective study of CES in the treatment of alcohol, drug and nicotine addiction, acute and chronic withdrawal symptoms were diminished, normal sleep patterns were restored more rapidly and more patients remained addiction-free following regular CES treatments compared to conventional psychopharmacological management. CES-treated patients had significantly fewer anxiety symptoms and higher quality of life measures compared to patients treated with prescription medications (Patterson 1984). Findings of several sham-controlled studies suggest that CES may significantly reduce the time needed for abstinent alcoholics and drug addicts to regain normal cognitive functioning following prolonged drug use or drinking (Smith 1982; Schmitt 1984). Regular CES treatments compare favorably with psychotherapy combined with relaxation training and biofeedback in reducing anxiety in patients abusing any substance (Overcash 1999).

In a 4-week double-blind study, 20 depressed alcoholics were randomized to receive 20 CES treatments at 70 to 80Hz, 4-7mA versus sham treatments. Patients who received CES treatments experienced significantly reduced anxiety by the end of the study. No adverse effects were reported (Krupitsky 1991). This finding suggests that CES might provide an effective non-pharmacological alternative treatment of anxiety in alcoholics while avoiding the risks of cross-tolerance and dependence associated with benzodiazepines. In contrast to established therapeutic benefits CES for managing symptoms of withdrawal from alcohol or opiates (my see my previous post), this approach does not facilitate smoking cessation or reduce nicotine withdrawal symptoms. A 5-day sham-controlled study randomized 51 smokers who were motivated to stop smoking to daily CES (30 microA, 2-msec, 10Hz pulsed signal) versus sham-CES (Pickworth 1997). At the end of the study there were no significant differences between CES and sham-CES in daily cigarettes smoked, smoking urges or nicotine withdrawal symptoms.

Infrequent mild adverse effects

A recently published review of safety issues associated with transcranial electrical stimulation found almost no adverse effects in over 18,000 sessions administered to healthy individuals, neurologic and psychiatric patients (Antal 2017). Infrequently reported transient adverse effects include mild tingling and burning sensations, headache and fatigue. The authors commented on 11 documented cases of possible mania induction in individuals diagnosed with depression however these cases could not be definitively linked to TES because of the small number of individuals enrolled in controlled trials.

Bottom line

There is evidence that regular CES treatments may reduce the severity of withdrawal and reduce time needed for return of normal cognitive functioning, restore normal sleep patterns, and reduce anxiety in the early stages of abstinence in individuals who abuse cocaine or alcohol. CES is widely used in rehabilitation centers and may provide an effective, affordable and practical alternative to conventional medication management of detoxification and withdrawal from alcohol, cocaine and heroin. However, CES does not reduce nicotine craving or withdrawal in individuals who are trying to stop smoking. I encourage you to find a therapist who is experienced in the use of CES if you are considering trying CES as part of a recovery program.

Neuroelectric Therapy for Managing Opioid Withdrawal

Urgent need for improved management of opioid withdrawal

This is the second post in a series on non-medication approaches for alcohol and drug abuse. Opioid addiction is a public health crisis in the U.S. It is estimated that as many as 36 million Americans abuse prescription opioid pain medications and approximately 500,000 are addicted to heroin. Effectively managing withdrawal and detoxification is critical to successful discontinuation of heroin or prescription opioid pain medications. Individuals undergoing opioid detox are more likely to leave treatment prematurely when opioid withdrawal symptoms are not adequately managed. This post reviews research findings on neuroelectric therapy, an approach that employs weak electrical current to mitigate symptoms of opioid withdrawal. A future post will review the evidence for neuroelectric therapy in managing alcohol withdrawal.

How neuroelectric therapy works

The term neuroelectric therapy is used to describe Cranial electrotherapy stimulation (CES) and Transcranial neuroelectric stimulation (TES), two techniques that use weak electrical current to reduce symptoms of opiate withdrawal such as depressed mood, pain, agitation and insomnia. TES is widely used in Germany for the management of withdrawal symptoms. Both approaches involve the application of weak electrical current to specific points on the scalp or ears at regular intervals during acute withdrawal from opiates, alcohol or nicotine. CES typically uses a single frequency setting, 100Hz. In contrast, TES treatments use multiple pulse frequencies and wave forms to lessen symptoms of detoxification depending on the particular substance of abuse and the stage of withdrawal that is being managed. In contrast to conventional pharmacological approaches, micro-current stimulation offers the important advantage of avoiding the use of other potentially addictive narcotics when managing symptoms of opiate withdrawal.

The mechanism of action by which weak electrical current reduces symptoms of alcohol and opiate withdrawal involves stimulation of release of endogenous brain opioid peptides including endorphins, enkephalins and others, and may be similar to the biological mechanism underlying electro-acupuncture. A recent study suggests that weak electrical current may modulate the activity of the amygdala or other limbic brain regions reducing pain and unpleasant emotions frequently associated with opioid withdrawal (Miranda & Taca 2017).

Inconsistent research findings

After decades of research findings on the efficacy of neuroelectric therapy for managing opioid withdrawal are inconsistent.

While some studies report significant benefit, other studies report negative or equivocal findings. In one small, open retrospective pilot study, charts were reviewed for 73 adults who had been managed for acute opioid withdrawal using a non-invasive electrical nerve stimulator (Miranda & Taca 2017). Most patients reported rapid reduction in withdrawal symptoms following 20 minutes of treatment which were sustained on 5-day follow-up. Following treatment with the nerve stimulator the majority of patients were successfully transitioned to conventional medication assisted therapy.

The mechanism of action is believed to involve stimulation of the amygdala (or other limbic structures) resulting in lessening of both physical discomfort and dysphoria that frequently accompany opioid withdrawal. Findings of another small study suggest that individuals who receive micro-current stimulation and methadone have less severe withdrawal symptoms than individuals using methadone alone (Bakhshani 2008). A 2013 review of controlled and uncontrolled studies and case reports on neuro-electric therapy for found ‘generally poor’ evidence for this approach in reducing opioid withdrawal and craving (Lincolnshire Knowledge and Research Service 2013).

Bottom line: more research needed 

Neuroelectric therapy should be regarded as potentially efficacious but provisional non-medication therapy for managing opioid withdrawal. Inconsistent research findings may reflect methodological differences in study design, the small number of sham-controlled studies, small study sizes and the absence of standardized treatment protocols. Pending confirmation by large well-designed sham-controlled studies neuroelectric therapy may prove to be a practical and affordable non-medication treatment of opioid withdrawal.

Alternative and Integrative Treatments of Alcohol and Drug Abuse

Reducing drinking and drug use and withdrawal symptoms without medications

This is the first post in a series on alternative and integrative approaches to alcohol and drug abuse. In this post I briefly comment on the limitations of mainstream conventional (pharmacologic and psychotherapeutic) treatments of alcohol and drug abuse and introduce readers to a variety of non-medication therapies that can help you cut down or stop drinking, reduce hangover symptoms, and control craving. Future posts will go into more depth on specific alternative and integrative approaches including concise reviews of research evidence, safety issues when they exist.

Limitations of mainstream conventional treatments of alcohol and drug abuse

Controlled studies and patient surveys show that existing conventional pharmacological and psychosocial treatments of alcohol and drug abuse and dependence have a mixed success record in helping individuals to stop drinking or abusing other substances and maintain abstinence. It is estimated that one year after stopping drinking or using a drug approximately one third continue resume drinking or abuse the same substance at the previous level, one third use the same or another substance but in a more controlled way, and roughly one third remain abstinent. Following the one year mark, abstinence rates continue to decline. There are no effective conventional treatments of cocaine addiction, and recovering alcoholics engaged in 12-step programs continue to experience high relapse rates. Only one third of recovering alcoholics who attend regular Alcoholics Anonymous meetings remain sober for more than one year.

Alternative and integrative treatments for alcohol and drug abuse

There is consistent positive evidence for the beneficial effects of lifestyle changes and a variety of non-pharmacologic treatments of alcohol and drug abuse. Reducing caffeine and refined sugar in the diet while increasing omega-3 consumption is associated with reduced relapse rates in abstinent alcoholics.

Supplementation with select natural products may have significant beneficial effects on reducing drinking and reducing withdrawal symptoms. For example, there is evidence that the amino acid taurine reduces alcohol withdrawal symptoms, SAMe (S-adenosylmethionine) reduces alcohol intake, and L-tryptophan reduces alcohol craving. The amino acid acetyl-L-carnitine may improve cognitive functioning in abstinent alcoholics.

Anti-oxidant vitamins taken before heavy drinking may reduce the severity of hang-over symptoms, and nicotinic acid may reduce the risk of developing dependence in chronic drinkers. Alcoholics who take magnesium and zinc supplements may mitigate the long-term neuropsychological consequences of chronic alcohol abuse. Emerging research findings suggest that some traditionally used herbs in Chinese medicine and Ayurveda are beneficial treatments of alcohol and drug abuse and dependence.

Relaxation, meditation and mindfulness training

There is evidence that the regular practice of relaxation techniques such as guided imagery and others, may reduce withdrawal symptoms following discontinuation of benzodiazepines. The regular practice of yoga, meditation or mindfulness training probably improves general functioning in alcoholics and may reduce the rate of relapse in abstinent alcoholics and addicts.

EEG biofeedback, virtual reality graded exposure therapy (VRGET) and acupuncture

EEG biofeedback using an alpha-theta training protocol probably reduces the rate of relapse in abstinent alcoholics. The application of weak electrical current to the brain may significantly reduce symptoms of alcohol and opiate withdrawal while improving associated symptoms of anxiety. Virtual reality graduated exposure therapy is emerging as a potentially effective non-drug therapy for reducing nicotine and cocaine craving. Regular exposure to dim morning light may reduce the risk of relapse in abstinent alcoholics. Some acupuncture protocols may reduce symptoms of withdrawal after chronic alcohol or cocaine abuse is discontinued.

I will review the evidence for these and other non-pharmacologic therapies in more detail in future posts. You can find a concise overview of alternative and integrative approaches to alcohol and drug abuse and practical methods for using them for alcohol or drug abuse, in my book “Alcohol and Drug Abuse: The Integrative Mental Health Solution.”

3 Top Ways to Fight the Winter Blues

Finding a non-pharmacologic treatment that works for you

This post is offered as a brief re-cap of highlights in my recent series of posts on complementary and alternative ways to fight the winter blues. Research studies consistently report the mood enhancing benefits of regular exercise, and two unique molecules that occur naturally in the human body that can be safely taken as supplements alone or in combination with an antidepressant: S-adenosylmethionine (SAMe) and dehydroepiandrosterone (DHEA). Below I briefly review the evidence for all three approaches. You can find detailed discussions of antidepressant mechanisms, analysis of research findings including links to studies cited, and comments on safety in my recent posts. On my website you can find practical information on a broad range of complementary, alternative and integrative ways to fight the winter blues, several full-text papers I’ve published over the years, and links to my books and e-books.

Regular exercise as an ‘antidepressant’ therapy

Findings of controlled trials report consistent mood-enhancing effects of regular exercise including both aerobic exercise and non-aerobic strengthening exercise. Regular aerobic exercise may improve cognitive functioning in chronically depressed individuals who often experience difficulties with thinking and memory. Meta-analyses of studies on exercise show consistent mood-enhancing benefits from exercise alone and improved response to antidepressants. Regular exercise may be as effective as St. John’s wort and other alternative treatments of depressed mood.

SAMe: effective for depressed mood and may reduce sexual side effects of antidepressants

Meta-analyses of placebo-controlled studies show that SAMe is as effective as many widely prescribed antidepressants when taken alone and improves overall response and may accelerate response rate when taken with an antidepressant. An important study published in the American Journal of Psychiatry reported that SAMe may also have significant mood enhancing benefits in individuals who do not respond to antidepressants. Combining SAMe with an antidepressant is a safe integrative way to treat depressed mood that may permit a reduction in the dose of a prescription antidepressant by as much as 30% in some cases. In addition to improving the efficacy of antidepressants, there is evidence that the adjunctive use of SAMe may reduce sexual side effects frequently caused by SSRIs and other antidepressants. Finally, taking SAMe 400mg twice daily together with an antidepressant may improve memory and other cognitive problems that often accompany depressed mood.

DHEA: mood enhancing and cognitive benefits and may improve sexual functioning

Like SAMe, DHEA taken alone may reduce the severity of depressed mood and can be safely used in conjunction with antidepressants increasing their efficacy. DHEA levels in the body and brain decline with normal aging, which may help explain some cases of late onset depression. Many individuals who respond to DHEA report improvements in sexual functioning.

DHEA may be an effective treatment of depressed mood individuals with HIV/AIDS, and may reduce symptoms of psychosis, anxiety and cognitive impairment all of which can occur together with depressed mood. Finally, there is some evidence that DHEA supplementation may reduces the rate of cognitive deterioration in Alzheimer’s disease and may improve anxiety and reduce the severity of psychotic symptoms in individuals diagnosed with schizophrenia.

Bottom line

If you’ve been struggling with depression, have had a disappointing response to antidepressants, or are looking for safe and effective non-pharmacologic approaches to boost the effectiveness of your antidepressant, think about adding exercise to your daily routine, or finding a quality brand of SAMe or DHEA. Before starting either supplement please take time to read the more detailed blogs posted in recent weeks.

Regular Exercise Improves Depressed Mood

This post is part of a series on non-medication treatments of depressed mood. Previous posts reviewed the evidence for folate, B-12, SAMe, omega-3 fatty acids, the amino acids L-tryptophan and 5-HTP, and the prohormone dehydroepiandrosterone (DHEA). This post is offered as a concise review of the evidence for the benefits of regular exercise in depression. You can find out more about a wide range of alternative and integrative approaches for depressed mood and other mental health problems on my website

How exercise improves depressed mood

The beneficial mood-elevating effects of exercise are probably related to short-term transient responses in the brain immediately following exercise, as well as long-term changes following two or more periods of exercise. Findings of animal and human studies suggest that both the immediate and long-term beneficial effects of exercise on mood are mediated by multiple factors that increase brain levels of mood-elevating endorphins, dopamine, norepinephrine, and serotonin, promote the development of new neurons in the brain (i.e. neurogenesis), reduce oxidative stress, and enhance immune functioning (Schuch 2016).  Findings of a recent fMRI pilot study suggest that regular exercise may promote increased neuroplasticity in certain brain regions, resulting in improved mood (Gourgouvelis 2017).

In addition to the direct and indirect effects of exercise on brain function, regular exercise also enhances self-sufficiency and ensures positive social interactions with other people. It is difficult to separate beneficial effects of exercise from other lifestyle factors, and it is possible that exercise contributes to overall feelings of wellness while not having specific mood elevating effects. Finally, regular exercise has been shown to improve sleep quality in individuals who do not respond to antidepressants (Rethorst 2013). This may be a significant benefit of exercise on overall resilience and day to day functioning in view of the high prevalence rate of insomnia in chronically depressed individuals.

Review of research findings

The following section is a brief review of research findings on exercise as a stand-alone therapy for depressed mood, and as an ‘add-on’ therapy for individuals taking an antidepressant, engaging in cognitive behavioral therapy, or using bright light exposure therapy.

Mood enhancing benefits of regular exercise 

Findings of controlled trials and systematic reviews report consistent mood-enhancing effects of regular exercise. Individuals who are less sedentary have a reduced risk of both depressed mood and cardiovascular disease (Schuch 2017). Both aerobic exercise and non-aerobic strengthening exercises are believed to be equally efficacious. The optimum duration and frequency of exercise needed to improve depressed mood have not yet been determined but probably vary with age and conditioning. Regular aerobic exercise may improve cognitive functioning in chronically depressed individuals who often experience difficulties with thinking and memory (Oertel-Knochel 2014).

Regular exercise as an ‘add-on’ therapy to antidepressants and other treatments

A recent meta-analysis of controlled studies (977 total subjects) on exercise used either as a single intervention or in combination with antidepressants reported that regular exercise has consistent beneficial effects on depressed mood (Kvam 2016). A systematic review of studies on exercise as an add-on therapy in individuals diagnosed with major depressive disorder found that depressed individuals who exercise regularly respond consistently better than individuals who take an antidepressant but do not exercise (Mura 2014).

Adding regular exercise to ongoing antidepressant and cognitive therapy improves treatment response (Gourgouvelis 2018). Moderately depressed individuals who exercise in addition to receiving regular cognitive behavioral therapy (CBT) are less depressed and report less frequent suicidal thoughts compared to individuals engaged in CBT only (Abdollahi 2017).  Antidepressants and exercise probably have equivalent effects on moderate depressed mood (Blumenthal 2007). The therapeutic benefits of regular exercise may also be comparable to validated complementary and alternative (CAM) treatments of depressed mood such as St. John’s Wort (Hypericum perforatum) (Ernst 1998).

Depressed patients who exercise in a brightly lit (2500 to 4000 lux) indoor environment experience more significant improvements in mood and greater feelings of vitality compared to depressed individuals who exercise indoors in ordinary room light (400 to 600 lux) (Partonen 1998). Depressed women patients who combined exercise with bright light exposure while taking a daily vitamin regimen reported significant improvements in mood (Brown 2001).

Safety considerations

Individuals who have chronic pain conditions, heart disease, or other medical problems that might limit the amount of exercise they can do should consult with their family doctor, cardiologist, or other qualified health care provider before starting a regular exercise program or increasing their current level of activity.

Bottom line

Regular exercise has established mood-enhancing benefits in depressed individuals that may be equivalent to cognitive therapy. Regular exercise improves overall life quality and improves cognitive functioning and sleep quality—problems that often accompany chronic depressed mood. Combining regular exercise with an antidepressant enhances antidepressant response. Regular exercise may also enhance response to bright light exposure therapy and select alternative therapies. As exercise has established beneficial effects on the heart and body everyone struggling with depression should be encouraged to engage in a regular exercise program (i.e., unless a medical problem limits their activity).

Consider Acupuncture for Fighting the Winter Blues

This post is part of a series on alternative and integrative treatments of depressed mood. Previous posts in the series reviewed research findings on anti-depressant benefits of SAMe, folate, vitamin B-12, omega-3s, DHEA, bright light exposure therapy, and exercise. This post is on acupuncture as a treatment of depressed mood. Acupuncture has been a central part of Chinese medicine for millennia and is widely used around the world to treat a variety of medical and mental health problems.

Mechanism of action

From a Western medical perspective the antidepressant effects of acupuncture may be mediated by nerve impulses transmitted at the point of needle insertion in the skin to the hypothalamus and other brain regions stimulating the release of norepinephrine, serotonin, dopamine, β-endorphin, enkephalin and possibly other neurotransmitters. According to Chinese medical theory, symptoms of depressed mood reflect deficiencies or imbalances in qi energy in certain meridians or organs.

Review of research

Findings of several sham-controlled double-blind studies support that acupuncture, including conventional manual acupuncture, electroacupuncture, laser acupuncture, and ear acupuncture (i.e. ariculotherapy) has antidepressant effects, however other sham-controlled studies report negative or equivocal results. These differences may reflect methodological problems inherent in designing studies on acupuncture related to heterogeneity in the severity of depressive mood symptoms being treated, high rates of comorbidity in many studies, concurrent use of other alternative therapies or medications in patients receiving acupuncture, and the use of different acupuncture treatment protocols depending on the energetic formulation (MacPherson 2004).

A meta-analysis of 13 studies comparing acupuncture vs an antidepressant plus acupuncture in in depression found that individuals receiving combined treatment responded better–and more rapidly– compared to individuals treated with an antidepressant alone (Chan 2015). The authors of a systematic review on acupuncture for depression concluded reported that acupuncture significantly reduces the severity of depressed mood symptoms (Wang 2008). However, the authors of a subsequent systematic review that included more studies found low quality evidence for an antidepressant effect of acupuncture (Smith 2018) when used alone or in conjunction with an antidepressant. The authors commented that significant variations in outcomes of individual studies may depend on differences in study design, the severity of depressive mood symptoms being treated, the acupuncture protocol used, and antidepressant medication being compared to acupuncture. In addition to the above factors, findings of meta-analyses may  also reflect cultural and ideological differences between researchers in different countries as well as differences in publication bias in medical journals published in China and Western countries.

Findings of a small double-blind sham-controlled study suggested that traditional manual acupuncture (ie, in the absence of electrical current) may be an effective treatment of severely depressed outpatients (Allen 1998). By the end of this 8-week study 68% of 33 female outpatients being treated with an acupuncture protocol directed at depressed mood had achieved full remission. The significance of these findings is limited by the fact that depressed women patients who were not receiving any treatment in a wait-list group showed equivalent improvement in depressed mood.

In a large six week multi-center study 241 depressed inpatients were randomized to receive electro-acupuncture plus placebo versus electro-acupuncture plus the antidepressant amitriptyline (Luo 1998). Both groups experienced equivalent improvement in depressed mood. It is interesting that patients treated with electro-acupuncture had significantly elevated plasma norepinephrine concentrations following a six-week course of treatment consistent with the hypothesis that electro-acupuncture may stimulate release of norepinephrine in the brain. Depressed patients who failed to respond to electro-acupuncture did not show significant changes in serum norepinephrine levels. Findings of a several studies support that acupuncture is a safe and effective treatment of depressed mood in pregnant women (Manber 2004; Sniezek 2013). In addition to its beneficial effects as an add-on therapy, emerging findings suggest that acupuncture may reduce the incidence of sexual side effects to antidepressants (Wu 2012).

A recent innovation in acupuncture uses computer-guided modulation of the frequency and waveform of the current delivered through acupuncture needles. Findings from open trials of computer-controlled electro-acupuncture (CCEA) suggest that high frequencies (1,000 Hz) yield responses in depressed patients that are superior to both conventional acupuncture and electro-acupuncture (Luo 1996).

Few safety issues

Acupuncture generally causes transient minor side effects such as soreness and bruising. A meta-analysis of studies of complications related to acupuncture identified infrequent cases of infection with HIV, hepatitis B and C due to use non-sterilized needles. Rare cases of pneumothorax and cardiac tamponade have been reported as a result of accidental puncturing of lungs or the pericardium (Ernst 1997; Wang 2018).

Bottom line

After decades of research, the evidence for acupuncture as a stand-alone therapy for depressed mood remains inconsistent however increasing numbers of well designed sham-controlled studies show efficacy. Differences in outcomes in different studies can probably be explained by the large variety of acupuncture techniques (manual, electroacupuncture, ear acupuncture and laser acupuncture) and protocols used, as well as subtle psychological, cultural and biological factors that translate into response differences and are difficult to characterize in Western medical terms. Accumulating research findings suggest that acupuncture may have significant adjunctive effects when combined with antidepressant therapy. Many studies support that acupuncture is a safe and effective treatment of major depressive disorder in woman and emerging findings suggest that acupuncture may help reduce the incidence of side effects caused by SSRIs and other antidepressants, including sexual side effects.

On the basis of the above, acupuncture should be regarded as a reasonable choice for depressed individuals who fail to respond to antidepressants, pregnant depressed women and for depressed individuals who are seeking non-pharmacologic ways to deal with medication side effects. 

To find out more about evidence-based alternative and integrative treatments of depressed mood check out my e-book “Depression: The Integrative Mental Health Solution.” 

Fighting the Winter Blues with DHEA

Fighting the winter blues with DHEA

This is the sixth in a series of posts on complementary and alternative therapies for depressed mood. Previous posts reviewed the evidence for SAMe, bright light exposure therapy, omega-3 fatty acids, and folate. The topic of this post is dehydroepiandrosterone (DHEA) a molecule that plays many key roles in the human body and brain that has been extensively investigated for its antidepressant and cognitive enhancing benefits.

Multiple mechanisms of action

Dehydroepiandrosterone (DHEA) is a prohormone (i.e. a precursor of both male and female sex hormones) that occurs naturally in the body and brain and plays key roles in mood regulation and the body’s stress response, and has general neuroprotective, antiinflammatory and anti-oxidant effects.  DHEA and a related molecule (DHEA-S) are both manufactured in the adrenal cortex and testes, and are later converted to androgens and estrogens–the male and female sex hormones–in peripheral tissues. DHEA-S is the sulfonated form of DHEA and the most abundant steroid hormone in the body. The antidepressant mechanism of DHEA has not been fully elucidated but may involve androgen receptors, estrogen receptors, or well defined neurotransmitter systems including serotonin, GABA, NMDA and norepinephrine. Estrogen manufactured from DHEA affects the synthesis and binding of serotonin at multiple receptors sites. A recent study found that elevated DHEA-S serum levels correlated with higher rates of response to SSRI antidepressants consistent with research findings that supplementation with DHEA has antidepressant benefits and significantly enhances antidepressant efficacy (Hough et al 2017).

Promising research findings when taken alone or together with an antidepressant

Research findings show that DHEA supplementation alone may reduce the severity of depressed mood and can be safely used in conjunction with antidepressants increasing their efficacy. Blood levels of DHEA decline with normal aging. An early study found that physiological replacement doses of DHEA (ie, 30 to 90mg/day, a dose range corresponding to DHEA serum levels that are normal in people younger than age 40) may improve mood in middle-aged or elderly depressed patients (Wolkowitz et al. 1997).

This above findings are consistent with the findings of a small randomized placebo-controlled trial in which individuals with mid-life onset depression experienced significant and sustained improvements in mood following several weeks of supplementation with DHEA (Schmidt et al 2005).  In the study 46 moderately depressed adults were randomized to DHEA 90mg/day for three weeks followed by DHEA 450mg/day in three equal doses, for three weeks versus placebo. None of the patients used antidepressants concurrently. A 50% or greater reduction in depressive symptoms was observed in the majority of patients in the DHEA group, which also reported improvements in baseline sexual functioning. Significantly, most patients who responded to DHEA remained asymptomatic at 12 months follow-up.

Two systematic reviews support that DHEA is an effective monotherapy for depressed mood and may be safely combined with antidepressants augmenting their efficacy (Peixoto et al 2018; Peixoto et al 2014). Research findings on DHEA in depressed mood are limited by the small size of many studies, differences in dosages used, and heterogeneous study designs.

DHEA for depressed mood in HIV/AIDS, Alzheimer’s disease and schizophrenia

DHEA may also be an effective treatment of depressed mood individuals with HIV/AIDS. In one study depressed HIV positive patients experienced significant improvements in mood and fatigue when taking DHEA 200 to 500mg/day (Rabkin 2000). Serum testosterone levels and CD4 T-cell counts were not affected. Psychotic or demented patients often experience significant co-morbid depressed mood. In addition to its established antidepressant benefits, emerging findings suggest that DHEA may also reduce symptoms of psychosis, anxiety and cognitive impairment all of which can occur together with depressed mood.

Research findings suggest that DHEA supplementation may reduces the rate of cognitive deterioration in Alzheimer’s disease (Knopman 2003), and may improve anxiety and negative psychotic symptoms (i.e., apathy, withdrawal, paucity of thought) in individuals diagnosed with schizophrenia. In a double-blind placebo-controlled study 30 inpatients diagnosed with schizophrenia treated with DHEA 100mg/day in addition to their antipsychotic medications experienced significant improvements in depressed mood, anxiety and negative psychotic symptoms (Strous 2003). For unclear reasons, women improved more than men.

Safety issues

Most individuals who take DHEA at doses that have been shown to reduce the severity of depressed mood report few mild adverse effects. Case reports show that DHEA can cause hirsutism (i.e. abnormal hair growth) and acne and can interfere with normal blood clotting. DHEA may promote cancer in women who have a history of estrogen receptor positive breast cancer, and should be avoided in this population. However, a metabolite of DHEA called 7-keto-DHEA is not converted into androgens or estrogens and can probably be safely used in this population. Preliminary findings suggest that DHEA supplementation may increase the risk of prostate cancer in men with early or undetected prostate cancer (Arnold 2005).

Bottom line

At dosages established to be effective against depressed mood DHEA has few adverse effects. Combining DHEA with psychiatric medications is a safe and reasonable integrative approach in depressed individuals who fail to respond–or have a partial response–to antidepressant therapy, and in depressed individuals with co-occurring anxiety, psychosis or cognitive symptoms. The beneficial effects of DHEA on libido and sexual functioning is a significant added benefit of DHEA in view of the high percentage of depressed individuals who report reduced libido due to depressed mood or the side effects of antidepressants. Finally, DHEA should be considered when depressed mood occurs together with anxiety, psychosis and cognitive impairment including in patients diagnosed with schizophrenia and Alzheimer’s disease. .

Further research is needed to replicate the findings reported in this post, evaluate the efficacy of DHEA as a monotherapy for severe depressed mood, further elucidate the mechanism for a synergistic or independent antidepressant effect of DHEA and determine optimal safe dosing strategies.

Omega3s have established mood enhancing benefits and boost the effectiveness of antidepressants

This is the fifth in a series of posts on non-pharmacologic treatments of depressed mood. Previous posts briefly reviewed research findings on S-adenosylmethionine (SAMe) and folate. This post is offered as a concise review of omega-3 essential fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the treatment of depressed mood.

Multiple mechanisms

Epidemiologic studies have found an inverse relationship between consumption of fish and other foods high in omega-3 fatty acids and the prevalence of depression suggesting that individuals who consume foods richer in omega-3s are at reduced risk of developing depressed mood. Human and animal studies point to several mechanisms of action underlying the antidepressant effects of omega-3 fatty acids, including increased CNS serotonin activity, anti-inflammatory effects, suppression of phosphatidyl-inositol second messenger activity, and possibly increased heart rate variability.

In addition to the above mechanisms, another proposed mechanism of action that may be similar to that of antidepressants, including SSRIs and older so-called ‘tricyclic’ antidepressants, involves the suppression of pro-inflammatory cytokine release by immune cells, resulting in beneficial changes in the brain that manifest as improved mood (Maes 1998). Evidence in support of an anti-inflammatory mechanism of omega-3s is consistent with the observation that increased production of pro-inflammatory cytokines takes place in the initial or “acute phase” of severe depressed mood (Maes 1996). Further, animal studies show that direct administration of pro-inflammatory cytokines into the brain causes dysregulation in serotonin metabolism that mirrors changes observed in depressed individuals. Reports that Omega-3 fatty acids may reduce the incidence of coronary artery disease by influencing the production of pro-inflammatory cytokines in the heart may help to explain the observed correlation between heart disease and major depressive disorder.

Research highlights

Findings of studies on antidepressant effects of omega-3s when used alone or when taken adjunctively with an antidepressant are highly inconsistent, however, over time there has been a trend toward more positive findings of well designed placebo-controlled trials. In some studies patients who had previously been refractory to antidepressants improved significantly when Omega-3s were added to their antidepressant.  Most studies support that EPA has greater antidepressant efficacy than DHA both alone and when used in combination with an antidepressant. There is still no consensus on an effective antidepressant dose of EPA; however, it is probably at least 2gm/day typically taken in divided doses with food for optimal absorption.

Findings on DHA in depressed are highly inconsistent possibly reflecting complex relationships between ratios of Omega-3s and other fatty acids (i.e., Omega-6) in the blood and brain and associated anti-inflammatory effects. In a small double-blind study on the efficacy of DHA alone for severe depressed mood patients treated with DHA 2g/day versus a placebo improved at the same rate (Marangell 2003). However, a subsequent DHA augmentation pilot study found an inverse correlation between dose and antidepressant response, with patients receiving 1gm/day reporting significantly greater improvement in depressive mood symptoms compared to individuals taking DHA at doses of 2gm/day and 4gm/day ( Mischoulon 2008). The authors speculated that an optimal ‘therapeutic window’ may take place when a dose of DHA or EPA results in changes in ratios of omega-3s (which have anti-inflammatory effects) to omega-6 fatty acids (which are pro-inflammatory) in the blood needed to achieve an ‘optimal’ balance between pro- and anti-inflammatory forces.

A meta-analysis of studies on omega-3 supplementation alone found consistent anti-depressant benefits of omega-3 supplementation in individuals diagnosed with major depressive disorder, in depressed individuals who were not diagnosed with MDD, but not in women diagnosed with prenatal depression, or in children and adolescents (Grosso et al 2014). A meta-analysis of 241 placebo-controlled studies on EPA, DHA or combined EPA/DHA augmentation of antidepressants found greater benefits with EPA and combined EPA/DHA; however, the authors reported that their findings were limited by methodological flaws in many studies, heterogeneous study designs, small study sizes, short study duration and (in some cases) evidence of publication bias (Martins 2009).

The above findings support the use of EPA in combination with antidepressants, including bipolar depressed patients and patients who are refractory to antidepressants. It remains unclear whether EPA (or specific ratios of EPA to DHA or other fatty acids) has an independent antidepressant effect or possibly enhances the efficacy of antidepressants via second messenger systems in a manner that is similar to the postulated mechanism for lithium augmentation (Nemets 2002).

Unanswered questions

Many questions about fatty acid composition, optimal dosing strategies and treatment duration have not been answered. Confirmation of the size of an augmentation effect in individuals taking antidepressants and further clarification of the antidepressant mechanism(s) of action of essential fatty acids will require large, long-term placebo-controlled trials designed to answer these questions.

Side effects and safety issues

Gastrointestinal side effects have been reported and Omega-3s may interfere with glucose metabolism in diabetic patients (Glauber 1988). There is one case report of increased bleeding risk when Omega-3 fatty acids are used together with coumadin (Buckley 2004).

Bottom line

Supplementation with EPA may enhance response to available antidepressants. EPA may be safely used in combination with antidepressants and other psychotropic medications. Omega-3s have established cardiovascular benefits and are well tolerated. The majority of people who take EPA at dosages recommended for depressed mood report mild or no adverse effects. On the basis of available data, depressed patients should be encouraged to take EPA (1 to 2g/day) as an augmentation strategy in conjunction with their current antidepressant regimen. Diabetics and individuals taking Coumadin or other anticoagulant medications should consult with their physician before considering taking omega-3s. 

Bright light exposure may improve seasonal depressed mood: more studies are needed

Regular morning exposure to bright light may improve seasonal depressed mood

This is the third post in a series on non-pharmacologic treatments of depressed mood. Previous posts provided brief reviews of the evidence for S-adenosylmethionine (SAMe) and folate. This post is offered as a concise discussion of bright light exposure therapy as a treatment of depressed mood. In addition to commenting on findings of individual studies I comment on the disparity in meta-analysis findings and the resulting debate on the efficacy of bright light therapy.

Mechanism of action is probably multi-factorial 

The mood enhancing benefits of bright light are probably related to many mechanisms of action that affect regulation of the synthesis of melatonin and neurotransmitters, especially the monamine neurotransmitters serotonin, dopamine and norepinephrine. Recent theoretical work suggests that the beneficial effects of light on the body and brain may be consistent with meridian theory in Chinese medicine (Cocilovo 1999).

Many studies support that exposure to bright light (10,000 lux) in the early morning, for one to two hours daily over several weeks (10,000 lux) has therapeutic effects in moderately or severely depressed patients. This effect is especially robust in patients who report recurring seasonal depressed mood changes–so-called seasonal affective disorder (SAD).

Small studies, short duration and methodological differences limit findings

Many studies report that morning exposure and evening exposure to bright light are probably equally effective in seasonal depressed mood however there are reports of insomnia with evening exposure. In addition to artificial full-spectrum bright light, exposure to natural sunlight, especially in the early morning, also has a significant anti-depressant effect, and may reduce the length of hospital stays in severely depressed bipolar inpatients (Benedetti 2001). Findings of a randomized double-blind study (89 total subjects) suggest that bright light delivered transcranially by LED inserted into the ear canals may have both antidepressant and anti-anxiety benefits in individuals diagnosed with seasonal affective disorder (Jurvelin 2014).

Findings of a small randomized trial suggest that bright light therapy may be an effective alternative to antidepressants in pregnant depressed women (Epperson 2004). In another study depressed patients who exercised regularly improved more when exposed to bright light than ordinary room light (Partonen 1998). A study published in the Journal of Affective Disorders in 2018 found that individuals diagnosed with seasonal affective disorder randomized to bright full spectrum exposure vs narrow spectrum low intensity blue light reported equivalent improvements in depressed mood symptoms (Meesters 2018).

Meta-analyses report conflicting findings

Although the above studies and many other controlled studies published in the peer-reviewed medical journal literature have reported beneficial effects of bright light exposure on seasonal depressed mood–and in some cases non-seasonal depressed mood, the conclusions of meta-analyses are inconsistent. For example, in an early meta-analysis Golden et al (Golden 2005) reported on large therapeutic benefits (i.e., a large ‘effect size’) of bright light exposure vs sham. The authors concluded that bright light exposure or dawn simulation for seasonal depressed mood, and bright light exposure (but not dawn simulation) for non-seasonal depression has comparable efficacy to conventional antidepressants (Golden 2005).  However, a more recent meta-analysis using more stringent selection criteria found only equivocal evidence in support of bright light exposure for depressed mood (Martensson 2015) arguing that findings of most studies are limited by small size, short duration and methodological differences in terms of light intensity, exposure duration, light source and wavelength examined, etc. Martensson et al also pointed out that selection bias in the Golden et al meta-analysis had led to unsubstantiated claims on the basis of 3 very small studies reporting positive outcomes.

Side effects can include headaches, insomnia and nausea

Some patients exposed to bright morning light 10,000 lux on a regular basis report transient side effects including mild jitteriness or headaches, and mild nausea. Sporadic cases of hypomania have been reported, especially in winter depressives or Bipolar patients exposed to early morning bright light. Almost two thirds of patients who use bright light exposure therapy in the evening report insomnia. Because of the risk of insomnia with evening bright light exposure, everyone who considering the use of bright light exposure to treat depressed mood should do so in the morning only.

Bottom line

Despite decades of research on full spectrum bright light (and more recently, dim blue light) exposure as a treatment of seasonal depressed mood, there is still no consensus among researchers on the antidepressant efficacy of this therapy. The wide disparity in reported outcomes reflects methodological differences in study designs, and suggests that factors that influence response to bright light exposure may not yet be adequately characterized. These factors may include the relative intensity of light, exposure duration, timing of exposure, frequency of exposure and wavelength. In addition, variation between individuals undergoing bright light therapy such as genetic, epigenetic and other poorly characterized inter-individual differences may help explain the disparity in response. Large prospective studies identifying and controlling for these factors are needed to elucidate the complex mechanisms of light therapy and to clarify its potential antidepressant effects.