Is Melatonin Safe With Antidepressants?

Sleep disorders are commonly associated with psychiatric conditions such as depression and bipolar disorder. Consequently, it is not uncommon for these patients to seek additional drug or nondrug therapy to facilitate a normal sleep pattern. While doctors usually prescribe traditional sleep aids such situations, more and more patients are looking for more products “natural.” In recent years, there has been an upsurge in the use of nonprescription products such as melatonin and tryptophan. Many patients see these medications as good for the body because they are “natural” substances, but the potential drug interactions, side effects, and the counter should be considered. The fundamental purpose of pharmaceutical care is to get the right medication for the right person at the right strength for the right situation.

Basic questions should be posed to the patient: Why are you not sleeping? What are your sleep patterns and habits? Are you slow to sleep or to wake up fast?

Tryptophan is shown in the treatment of sleep disorders, because it acts as a precursor molecule of melatonin, a neurohormone that is responsible for regulating the sleep cycle It also has the advantage of not limiting or interfering with cognitive performance awakening from sleep, as some of the more traditional agents do sleep. This essential amino acid also acts as an immediate precursor of neurotransmitter serotonin metabolic, which regulates mood and emotion. Subsequent conversion of tryptophan to serotonin is what causes concern about concomitant use of this supplement with antidepressants.

Through a variety of mechanisms, most antidepressants increase the level of neurotransmitters (eg serotonin, dopamine, norepinephrine) in the nerve synapse. Therefore, if a patient is taking a selective serotonin reuptake inhibitor (SSRI) or monoamine oxidase inhibitor (MAOI) together with tryptophan, the level of serotonin in the synapse can be enhanced significantly. This could precipitate a pharmacodynamic interaction known as serotonin syndrome, which is characterized by agitation, confusion, delirium, tachycardia, diaphoresis, blood pressure fluctuations, and extrapyramidal side effects. These symptoms often take place within 2 hours, but they can be solved about 70% of the time within 24 hours simply to the termination of serotonergic drugs. In light of the potential seriousness of serotonin syndrome, which is documented in published case reports, patients should be advised against taking tryptophan concurrently with MAOIs or SSRIs.

Personnel should be aware that tryptophan is found in protein supplements commonly used combination too, so they should ask patients about any dietary supplements that can be taken.

Finally, patients with liver cirrhosis have an additional reason to avoid the use of tryptophan harmony with MAOIs or SSRIs. Tryptophan pyrrolase activity will be reduced by more than 20%, leading to higher levels of tryptophan and decreased clearance of amino acids. These patients are at an even higher risk for developing serotonin syndrome.

Melatonin is a natural product is known as a sleep aid, but it has shown benefit only in patients experiencing delayed sleep phase disorder initial quality or interrupted sleep. Melatonin is the end product in the metabolism of L-tryptophan and serotonin is converted by the enzyme S-adenosyl-L-methionine. Once it is formed, it is metabolized hepatically by two cytochrome P450 enzymes, CYP1A2 and 2C19.

Some antidepressants, mood stabilizers, antipsychotics and drugs that are commonly used for patients with bipolar depression are metabolized by CYP1A2 and / or 2C19 and in fact may be prohibitive or inducers of these hepatic enzymes. In particular, the biggest concern lies with the concurrent use of melatonin and fluvoxamine, which is metabolized primarily by CYP1A2 with a small contribution from 2C19. Fluvoxamine is a potent inhibitor of CYP1A2 and therefore will cause an increase in blood levels of endogenous melatonin and increase drowsiness during the day. Other antidepressants and antipsychotics that are CYP1A2 substrates and which may affect melatonin metabolism include amitriptyline clomipramine, mirtazapine, carbamazepine, chlorpromazine, perphenazine, trifluoperazine, clozapine, haloperidol, and olanzapine. Published case reports have also noted the relationship with fluoxetine (a CYP1A2 inhibitor may lead to psychotic symptoms), warfarin (decreased prothrombin time and increased minor bleeding), and zolpidem (increase drowsiness during the day, confusion, and mixed). Other classes of drugs that can interact with melatonin include antiplatelets / anticoagulants, oral hypoglycemic agents, antihypertensives, Anticonvulsants and sedatives.

In addition to reviewing the profile of prescription medicines to patients, staff should consider food and environmental substances that can enhance the metabolism of melatonin and lead to increased drowsiness during the day. Specifically, caffeine intake and cigarette smoking should be considered, such as caffeine and polycyclic aromatic hydrocarbons found in cigarette smoke induce CYP1A2 significantly.

Patient’s medical history is also important. Melatonin should be avoided in patients with a history of seizures, as it lowers the seizure threshold. It should also be avoided during pregnancy because of its potential to alter pituitary-ovarian function, induce uterine contractions, or cause developmental disorders in the fetus.

Finally, patients should be advised that natural products are not always produced in accordance with accepted standards of production. For example, some brands of melatonin were found to contain impurities. In 1989, the FDA recalled products containing L-tryptophan, which were associated with 1543 cases of eosinophilia myalgia syndrome (EMS) and 28 deaths. A precursor known as 5-tryptophan hydroxytrytamine is now widely available, and similar impurities that lead to the development of EMS have been reported.

In conclusion, taking prescription antidepressants patients should be advised against taking melatonin or tryptophan to improve their sleep. In getting the right drug to the right patient, clarify the cause of sleep disturbance will help determine which medications or therapies should be used. For example, if it is secondary to psychiatric illness patients may resolve when the drugs used to treat the disease begin to take effect. On the other hand, the staff might consider setting an antidepressant that is known to have soothing properties, such as mirtazapine. Finally, some nonpharmacologic methods can help resolve a sleep disorder: good sleep hygiene, stimulus control, relaxation strategies, or cognitive behavioral therapy. If a sleep disorder persists, prescription sleep aids should be considered.