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St. Johns Wort Review - Anxiety and Depression

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St John’s wort is the most commonly prescribed herb in the treatment of depression. It has been demonstrated to be effective for treating major depressive disorders, especially among teenagers. However, there are concerns about the safety of St John’s wort. What are the side effects, adverse drug reactions and other dangers associated with St John’s wort? How dangerous is this herb compared to standard antidepressants? Read on to find out.

What is St John’s Wort?

St John’s wort is also known as Hypericum perforatum although the term is sometimes used for every member of the Hypericum plant family. This herb grows well in temperate and subtropical regions and it can be found in Europe, Asia and North America where it is either grown commercially or known as an invasive weed.

St John’s wort is most popularly known for its antidepressant properties. A review of available studies confirms this medicinal use of the herb.

The main phytochemicals in St John’s wort are:

  • Flavonoids such as rutin, quercetin, epigallocatechin and hyperoside
  • Phenolic acids such as chlorogenic acid
  • Naphthodianthrones such as hypericin
  • Phloroglucinols such as hyperforin

Of these, hypericin and hyperforin are believed to be the phytochemicals responsible for most of the medicinal benefits of St John’s wort including the antidepressant effects.

Hyperforin has been conclusively demonstrated to be responsible for this antidepressant effect of St John’s wort. However, there are clinical trials that indicate hypericin may also serve as an antidepressant.

The exact mechanism by which the bioactive phytochemicals of St John’s wort exert their antidepressant effect is unknown. Researchers currently believe that these phytochemicals share the same mechanism of action with the class of antidepressants known as SSRIs.

SSRIs or selective serotonin reuptake inhibitors block the removal of serotonin from the synaptic junctions between neurons. Serotonin is one of the key neurotransmitters that control mood.

Ideally, serotonin is removed from these junctions and returned back to the storage vesicles in the neurons from which it is released. This is done to prevent the repeated and prolonged stimulation of neurons by serotonin.

By preventing the removal of serotonin from the synaptic junctions, SSRIs prolong the action of serotonin, and by extension, improve mood and reduce depressive symptoms.

Because hyperforin and hypericin inhibit the reuptake of serotonin, they are also potent antidepressants.

Hyperforin can also block the reuptake of other neurotransmitters besides serotonin. It has been shown to inhibit the reuptake of dopamine and norepinephrine (two other neurotransmitters that contribute to the mood and are targeted by standard antidepressants).

How Effective is St John’s Wort?

Although a study by the National Center for Complementary and Alternative Medicine (NCCAM) found that St John’s wort demonstrated little to no effect as an antidepressant, the study has been widely criticized and faulted even by its authors.

Curiously, the same study indicated that Zoloft is not an effective antidepressant.

Other studies and extensive clinical data have, however, shown that St. John’s wort is indeed an effective treatment for major depressive disorders.

The most important scientific backing for the effectiveness of St John’s wort comes from the Cochrane Collaboration. In a review of 29 clinical trials done on the subject, the Cochrane reviewers concluded that St John’s wort

  • was indeed effective in the treatment of depression
  • was just as effective as standard antidepressants
  • produced far fewer side effects than these standard antidepressants (half the side effects of new SSRIs and one-fifth the side effects of tricyclic antidepressants)

A lot of new studies since the Cochrane review echo the same conclusions with one 2005 study published in the Journal of Clinical Psychopharmacology finding St John’s wort more effective than Prozac.

Although it has now been demonstrated that hyperforin is the most active phytochemical in St John’s wort, the majority of St John’s wort herbal supplements are still standardized by their hypericin content.

In the treatment of depression, the recommended dosage of St John’s wort supplements (extract standardized to 0.3% hypericin content) is 300 mg taken 3 times daily. However, as much as 1,800 mg daily has been safely used in clinical studies.

Besides its primary indication in the treatment of depression, St John’s wort extract is also used in the treatment of other disorders including Parkinson’s disease, memory impairment, and alcoholism.

Hyperforin has also been shown to have antibacterial and anti-inflammatory properties. As an antibacterial agent, St John’s wort extract is effective against gram-positive bacteria and can be applied topically to heal infected wounds, burns and broken skin.

In addition, the herbal extract is also used to treat inflammatory skin diseases.

St John’s wort is available in oral dosage forms such as capsules, tablets and powdered herb for infusion. It is also sold as a tincture. This herb can be sold alone or in combination with herbal products.

Side Effects of St John’s Wort

Although St John’s wort is a natural product, it is not without its side effects. Granted that it is safe in the right doses and well-tolerated by most people, St John’s wort is still a potent herb that contains very powerful phytochemicals that may be poisonous in certain doses.

The most common side effects of St John’s wort are actually mild. They include:

  • gastrointestinal symptoms such as nausea, constipation, and diarrhea
  • dizziness, confusion, and anxiety
  • headache and tiredness
  • sexual/erectile dysfunction
  • dry mouth

Rare side effects of the herb include:

  • skin rash and photosensitivity or skin hypersensitivity to light
  • blood clot disorders
  • liver disorders
  • psychiatric symptoms arising from overstimulation of neurotransmitter pathways in the brain

The common side effects can subside as the body develops a tolerance to the herb.

Some of the rare side effects can also be alleviated. For example, photosensitivity can be avoided in susceptible people with the application of sunscreen. Furthermore, reducing the dosage of the herb can remove psychiatric symptoms.

Perhaps the most serious side effect of St John’s wort is a form of serotonin toxicity known as serotonin syndrome.

Serotonin syndrome occurs when serotonin levels and/or activities are amplified by drugs or herbs that affect the serotonin pathway. The risk of serotonin syndrome with St John’s wort is actually low when the herb is used on its own. However, when combined with other serotonin drugs, serotonin toxicity represents a clear and avoidable danger.

Besides side effects, St John’s wort is also contraindicated for certain groups of people. For example, due to lack of the appropriate safety studies, St John’s wort is not recommended for pregnant and lactating women.

In addition, it should be avoided by those suffering from bipolar (manic-depressive) disorder, schizophrenia and Alzheimer’s disease.

Lastly, St John’s wort is not recommended for children except when prescribed and supervised by healthcare professionals. The herb is, however, effective for treating depression in adolescents. In fact, it is rather very effective for this age group.

Food Interactions with St John’s Wort

Besides drugs, certain foods may worsen the side effects of St John’s wort or interact with the herb to cause serious adverse effects and even another disorder.

Foods that should be avoided while taking St John’s wort include those containing tyramine. These include cheese, soy sauce, yeast, and eggplant.

Tyramine is a monoamine that is naturally synthesized from the amino acid, tyrosine (the precursor of monoamine neurotransmitters such as dopamine and serotonin).

Therefore, tyramine can be used by the body in the syntheses of monoamine neurotransmitters.

However, tyramine does not easily cross the blood-brain barrier, and so is not responsible for the psychoactive side effects of drugs that affect monoamine pathways. Even then, tyramine can cause serious side effects when combined with monoamine oxidase inhibitors such as the phytochemicals in St John’s wort.

The “cheese effect” is the result of such combination and it can also be triggered by other foods containing tyramine.

Tyramine obtained from a diet can displace norepinephrine from the neuronal vesicles where they are stored. Therefore, when combined with monoamine oxidase inhibitors, headache, migraine, and hypertensive crisis may result.

Drug Interactions with St John’s Wort

The most important drugs to avoid when taking St John’s wort are other antidepressants.

While not all antidepressants are contraindicated with St John’s wort, most of the important ones are. These include monoamine oxidase inhibitors like phenelzine; SSRIs like Prozac and Zoloft; SNRIs (serotonin and norepinephrine reuptake inhibitors) such as venlafaxine; and tricyclic antidepressants like amitriptyline.

The most common complication from combining St John’s wort with these drugs is serotonin syndrome.

Serotonin syndrome occurs when the serotonin levels in the central nervous system are too high. Depending on the doses of the combined drugs and the level of interaction, serotonin syndrome can cause varying degrees of symptoms.

The symptoms of serotonin syndrome include sweating, tremor, ataxia, nausea, hallucination, fever, confusion, hypertension, hypotension and even coma.

For mild symptoms, simply stopping St John’s wort and the other serotonin drug may be all that is needed. However, serious symptoms of serotonin syndrome should be treated as medical emergencies.

Other drugs to avoid taking with St John’s wort are:

  • Alcohol
  • Anti-allergy drugs
  • Antiarrhythmic drugs
  • Antibiotics such as ciprofloxacin and tetracycline
  • Antifungal drugs such as ketoconazole
  • Antiretroviral drugs
  • Benzodiazepines
  • Beta-blockers
  • Calcium channel blockers such as nifedipine
  • Cancer drugs
  • Lipid-lowering drugs including statins such as Lipitor
  • Immunosuppressants
  • Dextromethorphan, loperamide, digoxin, reserpine, warfarin, theophylline, omeprazole, and iron
  • Oral contraceptives
  • Psoralen medications
  • Sedative drugs and herbs
  • Triptans (migraine drugs)

How St John’s Wort Interacts with Drugs

Besides those drugs that act on the central nervous system (stimulants, opioids, antidepressants, and other serotonin drugs), St John’s wort interacts with the other drugs listed above by inducing the cytochrome P450 enzyme family.

More specifically, the cytochrome P450 enzymes induced are CYP3A4 and CYP2C9.

The phytochemicals in St John’s wort responsible for interacting with these enzymes are hyperforin and amentoflavone. Because the induced cytochrome enzymes are responsible for breaking down drugs, St John’s wort increases the metabolism of the affected drugs, and therefore, reduces their bioavailabilities and therapeutic effects.

St John’s wort may also affect the efficacies of drugs by inducing a transporter known as P-glycoprotein efflux transporter.

Unlike the cytochrome enzymes, this transporter does not increase the metabolism of drugs. Rather, it reduces their absorption and increases their clearance. These two actions reduce the concentrations of the drugs affected and also reduces the duration of action of the drugs.

Oral Contraceptives and St John’s Wort

Oral contraceptives are particularly affected by St John’s wort. The herb is able to reduce the effectiveness of these contraceptives and increase the risk of undesired pregnancy.

Hormonal contraceptives are generally affected in this way. To maintain contraception, non-hormone contraceptives are usually recommended as the birth control pills to use when also taking St John’s wort.

Withdrawal Symptoms

There have been reports of withdrawal symptoms from prolonged use of St John’s wort.

Since the herb shares similar mechanisms of action with standard antidepressants that cause withdrawal symptoms, discontinuation of St John’s wort should be done slowly.

While reports of withdrawal symptoms are not common, those who experience it report being dizzy, tense and feeling sick. To avoid such symptoms, the dose of St John’s wort should be tapered off when coming off the herb.





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