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5 HTP and SSRI

5 HTP and SSRIs both act on the serotonin pathway in the brain and they are both used to treat depression and other mood disorders. Is one better than the other? Can they both be combined? Read on to find out.
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What is 5 HTP?

5 HTP is also known as 5-hydroxytryptophan. It is a naturally occurring amino acids synthesized from another amino acid, L-tryptophan.

While L-tryptophan can be found in foods, there are no dietary sources of 5 HTP. Rather, its synthesis in the body depends solely on the level of L-tryptophan. However L-tryptophan makes up 1% of the amino acid content of dietary proteins.

In addition, tryptophan competes with other amino acids for absorption and transportation across the blood-brain barrier. Therefore, in the synthesis of 5 HTP, the transportation of tryptophan into the brain is the limiting step.

To improve tryptophan transportation into the central nervous system, proteins high in tryptophan such as meat, poultry, banana, papaya, potato and greens are recommended.

In addition, diets high in carbohydrates and low in proteins are better for tryptophan absorption because carbohydrates push amino acids into cells but leave tryptophan free to cross the blood-brain barrier.

The conversion of L-tryptophan to 5 HTP requires an enzyme called TPH or tryptophan hydroxylase.

To improve 5 HTP levels in the brain, it is given as a dietary supplement. 5 HTP is naturally produced in the seeds of Griffonia simplicifolia, a plant native to Africa.

Just like tryptophan, 5 HTP can cross the blood-brain barrier. In fact, it passes through this barrier more easily than tryptophan since it does not share the same transport mechanism with tryptophan, leucine, isoleucine and valine.

5 HTP is ultimately converted to serotonin or 5 HT in the brain, and all its effects are due to this compound.

5 HTP and Serotonin

Serotonin is a monoamine neurotransmitter made from 5 HTP in the central nervous system.

However, most of the serotonin produced in the body are found outside of the brain. 90% of the serotonin released in the body are found in the enterochromaffin cells of the gastrointestinal tract.

The platelet is responsible for storing and transporting serotonin outside the brain. Serotonin is needed in different parts of the body. Its effects can be seen in the cardiovascular, endocrine and musculoskeletal systems.

Serotonin is a vasoconstrictor and it is also a growth factor that speeds of wound healing. In addition, serotonin prompts the release of insulin-growth factor and it contributes to carbohydrate metabolism by promoting the release of insulin.

In the central nervous system, serotonin is responsible for controlling mood, sleep and appetite. It is also needed for learning and memory.

Because of the effects of serotonin in the central nervous system, changes in its levels in the brain can have profound effect. For example, low levels of serotonin may cause sleep disturbance, depression and weight gain through excessive eating.

However, serotonin cannot be directly ingested to supplement its production in the body. This is because serotonin does not cross the blood-brain barrier.

Therefore, instead of directly supplementing with serotonin, 5 HTP dietary supplements are taken to increase the level of serotonin in the brain.

Serotonin, Serotonin Receptors and Serotonin Drugs

Serotonin produces its effects by binding to serotonin receptors all over the body. There are 7 classes of serotonin receptors numbered from 5 HT1 to 5 HT7. Each of these classes has a family of receptor sub-types.

Serotonin receptors are also responsible for some of the actions of other neurotransmitters such as GABA, glutamate, norepinephrine, epinephrine, acetylcholine and dopamine.

Therefore, each receptor can either produce excitatory or inhibitory responses.

Serotonin receptors are also found in the endocrine receptors. For example, the secretion and actions of hormones such as cortisol, vasopressin, prolactin, oxytocin and substance P are mediated by these receptors.

This wide influence of the serotonergic system makes for a complex interplay, and it is the reason serotonin can produce strong and wide-ranging therapeutic and side effects in the body.

Drugs that act on the serotonergic system are varied. They include conventional medications, dietary supplements and herbal extracts.

Serotonin drugs can produce one or more of the effects listed in the table below.

Effects of Serotonin Drugs
  • Directly increase the production and secretion of serotonin
  • Inhibit the clearance of serotonin from receptor sites and nerve endings in order to allow serotonin to act longer at these sites
  • Inhibit the enzymes that break down serotonin to allow the neurotransmitter to work longer at receptor sites
  • Bind to serotonin receptors and mimic the effects of serotonin

What Are SSRIs?

SSRIs or selective serotonin re-uptake inhibitors refers to a number of antidepressants that act by preventing the clearance of serotonin from nerve endings.

These drugs are not only used to treat depression but also anxiety, panic disorders, obsessive compulsive disorders, stress disorders, eating disorders and chronic pain.

To fully understand how SSRIs work, an understanding of how signals are transmitter in the brain is needed.

Signal transmission in the brain happens between the two nerve cells that exchange chemical messengers or neurotransmitters like serotonin through the synapse which is a gap between the two cells.

The cell sending the information releases the neurotransmitter into the gap and this neurotransmitter stimulates the recipient cell and activates the receptor on the surface of the second cell.

A return mechanism located in the gap between the two cells takes up the neurotransmitter released into the synapse and returns most (90%) of the neurotransmitter back to the first cell sending the signal.

The process by which this return mechanism clears the neurotransmitter from the gap between the nerve cells and returns it to the sending cell is called reuptake. The return mechanism in the case of serotonin is a monoamine transporter.

Therefore, SSRIs blocks the monoamine transporter responsible for the reuptake of serotonin between nerve cells. This allows serotonin to stay longer in the gap between the nerve cells and have more time to stimulate serotonin receptors on recipient cells.

SSRIs, however, show even greater specificity by only inhibiting the monoamine transporter responsible for serotonin reuptake. It does not affect the actions of other monoamine neurotransmitters such as norepinephrine and dopamine.

In summary, SSRIs do not increase the production of serotonin like 5 HTP. Rather they amplify a weak signal at serotonin receptors. They cannot initiate these signals on their own.

Effects of SSRIs

A number of studies have demonstrated that SSRIs are most effective when used to treat severe depression. They are less effective when used to treat mild to moderate depression.

SSRIs are just one class of serotonin reuptake inhibitors. Selective serotonin reuptake enhancers are also selective serotonergic drugs used in the treatment of depression although their actions are opposite those of SSRIs.

Serotonin norepinephrine reuptake inhibitors and serotonin norepinephrine dopamine reuptake inhibitors are also serotonergic antidepressants although they are not as selective as SSRIs.

Popular examples of SSRIs include Prozac which contains fluoxetine and Zoloft which contains sertraline.

Other commonly prescribed SSRIs include citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox) and paroxetine (Paxil).

SSRIs generally take 6 – 8 weeks to reach their peak effectiveness although side effects usually presents earlier while the body adapts to the drugs.

SSRIs may be selective in action but they do cause some side effects (although these are fewer than the side effects of non-selective antidepressants).

The side effects of SSRIs include:

  • Headache
  • Nausea, diarrhea and vomiting
  • Dizziness, fatigue, insomnia and drowsiness
  • Changes in appetite, weight gain/loss
  • Vivid dreams and paresthesia
  • Renal impairment and urinary retention
  • Mania, dissociative and cognitive disorders and tremors

SSRIs are also required to carry a black box warning of increased risk of suicidal tendencies in children and adolescents.

SSRIs may also cause cardiovascular side effects but rarely.

Sexual dysfunction is another common complaint of SSRIs. For some, this happens while taking the drugs but for some it may persist after or start only after discontinuing the drugs.

SSRIs may cause physical dependence. Therefore, they should not be suddenly withdrawn especially after long-term therapy.

Simultaneous Use of 5 HTP and SSRIs

Since 5 HTP (increase serotonin synthesis) and SSRIs (prolongs serotonin action) affects the serotonergic system in different ways, some people may be tempted to combine both drugs to achieve better results especially in the treatment of depression. However, such combination is not encouraged because it is potentially dangerous.

When 5 HTP is combined with SSRIs, the combination may cause serotonin syndrome, a kind of serotonin toxicity.

While 5 HTP increases the production of serotonin in the brain, SSRIs will increase the time serotonin spends at nerve endings. This can lead to dangerous amplification of signals in the serotonergic system.

The symptoms of serotonin syndrome varies from mild to severe ones. While mild symptoms may get resolved within 24 hours of stopping both 5 HTP and SSRIs, severe symptoms may need medical intervention.

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


Symptoms such as hypertension and hyperthermia must be treated immediately; hypertension with hypertensive drugs and hyperthermia with cooling blankets and ice bath immersion (the high temperature associated with serotonin syndrome does not respond to antipyretic drugs since the temperature rise is due to hyperactivity of the muscles).

Serotonin receptor antagonists such as cyproheptadine can also be used to alleviate the symptoms of serotonin syndrome. Antagonists block serotonin receptors and prevent serotonin and SSRIs from bind to these receptors.

Sources


http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000938.htm

http://www.anxietyzone.com/glossary/selective_serotonin_reuptake_inhibitor.html

http://www.medical-hypotheses.com/article/S0306-9877(05)00068-X/abstract

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