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5 htp and Antidepressants

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5 HTP increases serotonin levels in the brain. Since antidepressants also increase serotonin transmission in the brain, 5 HTP supplements is an alternative to this class of drugs. Read on to find out the relative efficacy and safety of 5 HTP when compared to antidepressants.

What is 5 HTP?

5 HTP is also known as 5-hydroxytryptophan and a precursor of serotonin or 5 HT.

5 HTP is a naturally occurring amino acid made from an essential amino acid, L-tryptophan. Both amino acids can cross the blood-brain barrier but 5 HTP crosses more easily than tryptophan.

Even though 5 HTP crosses into the brain better than tryptophan, it has no dietary sources and therefore, cannot be obtained from foods. Instead, the body synthesizes 5 HTP from tryptophan found in foods like meat, poultry, papaya, banana, potato, pumpkin and greens.

However, of the 8 essential amino acids, L-tryptophan is found in the smallest amounts in food proteins.

It makes up an estimated 1% of dietary amino acids and because it competes with other amino acids for absorption into the brain, the extent of 5 HTP synthesis from dietary tryptophan is limited.

Even some of the tryptophan absorbed can be diverted to synthesized melatonin which is produced in the body by a pathway that shares some precursors with serotonin synthesis.

Therefore, tryptophan (dietary or supplement) is a poor source of serotonin.

Instead, 5 HTP can be directly taken in the form of dietary supplements. It is easily absorbed and crosses into the brain where it can be used to produce serotonin. The 5 HTP used in these supplements is extracted from the seeds of Griffonia simplicifolia, an African plant.

Since 5 HTP is exclusively transformed into serotonin in the body, all the effects of 5 HTP are due to serotonin.

5 HTP and Serotonin

Serotonin is a monoamine neurotransmitter naturally produced in the central nervous system and the gastrointestinal tract. Most (90%) of the serotonin produced in the body is synthesized in the enterochromaffin cells of the gut.

Outside the central nervous system, serotonin is stored in the platelets and is released from which it is released to serve as vasoconstrictor, stop blood clotting and promote wound healing. Therefore, serotonin has an important effect on the cardiovascular system.

Serotonin may serve as a neurotransmitter in the brain, but elsewhere it can serve as a growth factor.

It is also responsible for the release of insulin-like growth factor as well as hormones such as insulin. Other hormones controlled by serotonin (or rather, serotonin receptors) include cortisol, vasopressin, oxytocin, prolactin and substance P.

There are 7 classes of serotonin receptors numbered from 5 HT1 to 5 HT7. Each class has a family of receptor sub-types and are all similar except for 5 HT3.

Serotonin receptors are also partly responsible for the release of other neurotransmitters such as dopamine, glutamate, GABA, acetylcholine, norepinephrine and epinephrine. Therefore, 5 HT receptors can mediate both excitatory and inhibitory responses. This makes the serotonergic pathway complex.

In the brain, serotonin is the neurotransmitter responsible for mood, sleep and appetite. It also contributes to memory and learning.

Because serotonin levels and the activity of serotonergic pathway determines mood, serotonin drugs are commonly used as antidepressants to help improve mood.

Low serotonin levels may cause depression and other medical conditions such as incessant food cravings, weight gain and sleep disturbance. High levels of serotonin or hyperactivity of the serotonergic pathway, on the other hand, may cause a toxicity reaction called serotonin syndrome.

What Are Antidepressants?

Antidepressants are medications used to treat mood and anxiety disorders such as depression.

Strong narcotics such as opioids and amphetamines have antidepressant effects but are not usually recommended because of their addictive potential and strong effect. However, even though opioids are not usually used to treat depression, some of new ones (buprenorphine, for example) have been found to be effective where regular antidepressants fail to work.

Although they are primarily used for treating depression, antidepressants have other uses. They are commonly prescribed for treating eating disorders, chronic pain, OCD (obsessive compulsive disorder), ADHD (attention deficit hyperactivity disorder), anxiety disorders, snoring, migraine and even dysmenorrhea.

The major types of antidepressants are:

  • MAOIs or monoamine oxidase inhibitors
  • TCAs or tricyclic antidepressants
  • SSRIs or selective serotonin reuptake inhibitors
  • SNRIs or serotonin norepinephrine reuptake inhibitors

Other classes of antidepressants include:

  • NRIs or norepinephrine reuptake inhibitor
  • NaSSAs or noradrenergic and specific serotonergic antidepressants
  • NDRIs or norepinephrine dopamine reuptake inhibitors
  • NDDIs or norepinephrine dopamine disinhibitors
  • SSREs or selective serotonin reuptake enhancers

Other drug classes such as antipsychotics (in small doses) and benzodiazepines also have antidepressant effects. In addition, natural herbal extracts such as St. John’s Wort are also sometimes recommended for treating depression.

Most antidepressants do not have a rapid onset of action. They usually take as long as 2 – 6 weeks to show the first positive signs and can be taken for long-term therapy.

Antidepressants are not effective for 30 – 50% of depressed patients. For those that get better with treatment, long-term therapy may be required to prevent relapse. However, with time most antidepressants lose their efficacies.

Basically, antidepressants increase the levels of neurotransmitters such as serotonin, dopamine and norepinephrine. They do this either by preventing the degradation of these neurotransmitters by certain enzymes or blocking their removal from nerve endings.

Given the central role of serotonin in mood control, it is the most important target of antidepressants.

Antidepressants are not without their side effects. Each class of antidepressants has its own set of side effects.

For example, SSRIs cause nausea, headaches, agitation, erectile dysfunction, loss of libido and serotonin syndrome. Tricyclic antidepressants cause dry mouth, blurred vision, drowsiness, dizziness, skin rash, tremors, sexual and weight problems.

The periods at the beginning and at the end of antidepressant therapy are the most important and may require medical attention. At the beginning of antidepressant therapy, patients may experience worsening symptoms and even suicidal tendencies.

Similarly symptoms may worsen especially if antidepressants are stopped abruptly. Rather, a period of weaning during which the dose of the antidepressant is slowly reduced is advised.

5 HTP vs. Antidepressants

A number of small studies have been done to compare the efficacy of 5 HTP as an antidepressant against conventional antidepressants.

5 HTP has been shown in small groups of patients to produce the same level of therapeutic efficacy as SSRIs such as Prozac and Zoloft. These studies also show that 5 HTP is better tolerated than these antidepressants and that its side effects are mild and transient.

Generally, it is recommended that 5 HTP should not be taken alongside antidepressants especially those belonging to drug classes such as SSRIs, SNRIs, MAOIs and tricyclic antidepressants. 5 HTP should only be combined with antidepressants following the advice and under the supervision of a physician.

Because 5 HTP increases the levels of serotonin in the central nervous system, the combination of the supplement with antidepressants can dramatically increase serotonergic activities and cause a potentially lethal condition known as serotonin syndrome.

Serotonin Syndrome

Serotonin syndrome is a toxicity reaction with varying set of symptoms. Some of these are mild while others are life-threatening.

Because the symptoms of serotonin syndrome resemble those of other medical conditions caused by infections, intoxication, hormonal imbalance and metabolic dysfunction, it can be difficult to diagnose. However, a simple drug history should show any potential combination of serotonin drugs and/or supplements that may cause this syndrome.

Serotonin syndrome can cause a spectrum of symptoms, and because serotonin produces its effects in the central nervous system as well as cardiovascular, endocrine and musculoskeletal systems, the sum of side effects can proceed rapidly and should be treated as medical emergency.

Symptoms of Serotonin Syndrome

Cognitive – Hyperactivity, confusion, mania, headache and hallucination

Autonomic – Hypertension, hyperthermia, sweating, shivering, flushing and irregular heartbeat

Neuromuscular – Overactive reflexes, symmetrical twitching in the limbs, ataxia and tremor

Serotonin syndrome usually resolves within 24 hours of stopping the offending drugs (5 HTP and antidepressants). Symptoms such as hypothermia, hypertension, ataxia and mania may need urgent treatment.

Cyroheptadine, a serotonin receptor antagonist, is commonly used to block serotonin receptors and prevent the worsening of symptoms. However, its efficacy for this application has not been clinically proven.





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