Depression: Antidepressant Side Effects Hinder Long-Term Treatment
A Review of Side Effects and Alternative Therapies

Depression is the leading cause of disability in the United States, affecting more than 20 million people, or nearly 10 percent of all adult Americans aged 18-years or older. Depressive disorders occur nearly twice as often in women (12 percent) as men (7 percent), and in financial terms, ranks as one of the 10 most costly illnesses in the US, with cost estimates ranging upwards of $465 billion per year. Left untreated, depression is a serious medical disorder that can interfere with normal daily functions, erode friendships and family bonds, and severely disrupt lives.

Standard Antidepressant Treatment
Current medical treatment for depression favors prescription antidepressant drugs that work by altering the function of brain neurotransmitters, such as serotonin and norepinephrine. The older classes of antidepressant medications--the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)--were effective for some people, but carried a high risk of side effects, including tiredness, drowsiness, dry mouth, constipation, light headedness, low blood pressure, sweats, palpitations, and memory loss. Risk of toxic overdose with TCAs was also a serious problem.

The next generation of antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), were safer and more effective, but still caused unpleasant side effects in
some people, such as nervousness, nausea, mild constipation, inhibition of sexual orgasm, loss of sexual desire, and partial impotence. Now, researchers are developing a new generation of antidepressants--dual-action drugs known as serotonin and norepinephrine reuptake inhibitors (SNRIs)--that is hoped will have fewer side effects than current medications.


Side Effects Interfere with Treatment
While currently available antidepressants are often quite effective, a number of recent surveys reveal that unpleasant side effects can sometimes be serious enough to interfere with successful long-term treatment. In one survey conducted by the National Depressive and Manic-Depressive Association (National DMDA), the nations largest patient-led, advocacy organization, the majority of people being treated for depression reported unpleasant side effects and only modest improvement in their condition. The online survey, conducted on the National DMDA website during the summer of 1999, screened for participants who had been treated for depression. Members of all adult age ranges were represented, and three out of four respondents were female.

Of the 1,370 participants, less than one-third reported satisfaction with their treatment. In fact, side effects of current antidepressants were experienced by 80 percent of those surveyed. In fact, 17 percent of those surveyed stopped taking their medication due to side effects, and eight percent missed at least one dose per week. The most commonly reported side effect of medication was drowsiness, with 60 percent of medication-takers feeling tired. Other side effects include headaches, sleeplessness, agitation, nausea or other gastrointestinal problems and sexual dysfunction.

Most depressing was the finding that, despite treatment, 81 percent of those surveyed reported that depression still impaired their social life, 79 percent said it affected their family life, and 72 percent reported problems with their work performance. 'This survey gives a voice to many depression sufferers who cannot tolerate their antidepressant medication or arent satisfied with the improvement in symptoms,' said Lydia Lewis, executive director of the National DMDA. 'While we know that treatment works for more than 80% of those suffering from a depressive illness, we still urgently need new strategies for managing depression.

A second DMDA survey released this past January has turned up even more problems with antidepressant medication. The survey of 1,001 patients and nearly 900 primary care physicians found that 47 percent of patients reported side effects from medications. More startlingly, of those reporting side effects, 55 percent reported that they had stopped using prescribed drugs, and 17 percent reported skipping doses.

Clearly, the suffering caused by depression places a huge burden on individuals, families, and society. Faced with the ongoing problem of undesirable side effects from
current medical treatments, researchers continue to search for safer alternative approaches for treating depression and anxiety.

Alternative Treatments
Conventional medicine has traditionally viewed human health as a steady state. Recent scientific evidence suggests instead that the human body is in a constantly changing
and integrated state of flux, balanced by the rhythmic ebb and flow of hormones, neurotransmitters, enzymes, and receptor sensitivities.

Every living creature has normal daily (circadian) rhythms, such as the sleep/wake cycle, that are keyed to the earths day and night phases. Daily rhythms also affect the function of the lungs, cardiovascular system, kidneys, blood flow, muscular activity, and cognitive function. Humans also experience weekly, monthly and yearly cycles that subtly affect reproduction, immune function, and other systems.

Depression and anxiety often are the result of a disturbance (dysregulation) of multiple neurochemical and neuroendocrine systems. Although many neurochemicals are
secreted throughout the day, the amount secreted varies, with high peaks and low valleys occurring at regular intervals throughout the day and night.

Any imbalance in the normal amount or timing of neurochemical release can lead to a disruption of the internal biological clock (chronobiological desynchrony). This, in
turn, can lead to clinical depression and anxiety, and can contribute to migraine headaches, hypertension (high blood pressure), neurologic diseases, myopathy, and premature aging.


Syncholamine and Positrol
Our increasing awareness of the importance of chronobiologic factors in the normal functioning of the body is the basis for a natural approach to mental health based on rebalancing our biological rhythms. This is the thinking behind a revolutionary new form of chronotherapy for depression, anxiety, and bipolar disorders, sleep disturbances and other affective disorders. This approach consists of two different chronobiotic complexes designed to be used together to balance and restore normal circadian hormonal rhythms: Syncholamine and Positrol.

Syncholamine is designed to be taken during the early part of the day, when its ingredients help restore the neurohormone peaks that normally occur during this time. It contains the stimulatory amino acid catecholamine precursors L-phenylalanine and L-tyrosine, along with nutrient cofactors to synthesize norepinephrine, epinephrine, L-DOPA, and dopamine (Fig. 1). These nutrients also increase the concentrations of the endogenous (built-in) stimulant/antidepressant phenethylamine and the natural pain
relievers known as enkephalins.

Syncholamine also contains extracts of St. Johns wort (Hypericum perforatum), one of the most popular and effective natural antidepressant nutrients in use today. Many studies have shown that St. Johns wort can be effective in the treatment of depression, anxiety, apathy, sleep disturbances, insomnia, anorexia, and feelings of worthlessness. Even more impressive is the fact that St. Johns wort produces these results with minimal side effects.

St. Johns wort seems to work primarily by potentiating the effects of the catecholamines and indoleamines by its MAO-inhibiting properties. St. Johns worts MAO-inhibiting activity prevents monoamine oxidase from breaking down norepinephrine and serotonin, thus helping to amplify the cyclical peak that occurs during the morning hours. St. Johns wort also improves the signal produced by serotonin after it binds to its appropriate receptor site, an effect that is even more important in the evening. In still
another action, St. Johns wort mimics benzodiazepine anti-anxiety drugs (like Valium and Ativan) by binding gamma-aminobutyric acid (GABA) receptors.

Other ingredients in Syncholamine include pyroxidol-5-phosphate, the active form of vitamin B6 in the body, folic acid, and vitamin B12. The body requires vitamin B6 to
manufacture norepinephrine, dopamine, and serotonin, and to produce phenylethylamine from phenylalanine. Vitamin B6 levels have been found to be low in depressed patients. Moreover, studies show that supplementing vitamin B6 in people with affective disorders is associated with increased levels of NE and serotonin and relief of depression.

Folic acid and vitamin B12 are necessary for the synthesis of S-adenosylmethionine (SAMe), which is vital for neurotransmitter metabolism. A deficiency of either folic
acid or vitamin B12 may cause similar neurologic and psychiatric disturbances, including depression, dementia, and demyelinating myopathy. A folate deficiency, in particular, may specifically affect the metabolism of catecholamines and indoleamines and aggravate depressive disorders.

Folic acid and vitamins B6 and B12 are also required for the conversion of homocysteine to methionine. This prevents the accumulation of homocysteine, which has been
linked to the formation of atherosclerotic plaque in arteries as well as to neurotoxic effects that can produce neurologic and psychiatric disturbances.

Positrol is designed to be taken in the evening, when its ingredients help boost the normal nocturnal indoleamine peaks. It contains the neurotransmitter precursor 5-HTP, plus nutrient cofactors to synthesize serotonin and melatonin. Positrol also contains melatonin itself and St. Johns wort.

The body makes 5-HTP from the essential amino acid tryptophan and turns it into serotonin. Taking supplements containing 5-HTP raises the level of serotonin in the
brain, which can have profound effects on mood, behavior, and sleep patterns. Because serotonin is a circadian rhythm regulator, raising its levels at night promotes circadian synchrony. 5-HTP also boosts the levels of beta-endorphin and other neurotransmitters.

Numerous studies have demonstrated that the ingredients in Positrol can help relieve depression, anxiety, and obsessive-compulsive disorder. In one important comparative
study, 5-HTP was found to be as effective as an SSRI drug (fluvoxamine) in reducing depression, with fewer adverse effects. 5-HTP can also help counteract other symptoms of a serotonin deficiency, such as insomnia, overeating, SAD, and fibromyalgia. Taking Positrol in the evening helps maintain the bodys temporal organization, coordinating its individual endogenous oscillations with the environment. The result is the relief of major affective disorders, such as depression, bipolar disorder, anxiety and dementia.

Resynchronizing Mood Cycles
The combination of Syncholamine and Positrol represent a safe and natural approach to mental health, based on circadian synchronism and control of homeostasis. Taking
Syncholamine in the early part of the day, and Positrol toward the end of the day, produces a greater benefit than taking either product alone. Together these formulas act as timekeepers to resynchronize the bodys circadian rhythms, while promoting the proper circadian switching and functioning of the daytime energy production pathway and the nighttime sleep and repair pathway. In addition, these formulas may have anti-aging effects by normalizing neurotransmitter balance, thereby improving hypothalamic receptor sensitivity.

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How did we qualify them ?

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8. Wetterberg L. Melatonin and affective disorders. Ciba Found Symp. 1985;117:253-65.

9. Wahlund B, Grahn H, Saaf J, Wetterberg L. Affective disorder subtyped by psychomotor symptoms, monoamine oxidase, melatonin and cortisol: identification of patients with latent bipolar disorder [In Process Citation]. Eur Arch Psychiatry Clin Neurosci. 1998;248:215-24.

10. Beck-Friis J, von Rosen D, Kjellman BF, Ljunggren JG, Wetterberg L. Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects. Psychoneuroendocrinology. 1984;9:261-77.

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