Clinical Report-Drug Interaction Between Fluoxetin and Mirtazapine

July 23, 2012 Adverse Drug Reactions, Drug Interactions, Entertainment 55 comments , , ,

Clinical Case Report


Fluoxetin and Mirtazapine.

Date: July 8 2012

Place: Outpatient Pharmacy, 416 Hospital

Abstract and Introduction:

On the afternoon, July 8 2012 one male patient came to the outpatient pharmacy to take his drug. The phyisican prescribed fluoxetin accompanied by mirtazapine. I checked these two drugs in drug interaction checker and drug interactions were found between fluoxetine and mirtazapine – Potential for dangerous interaction ( may causes serotonin syndrome, although serotonin is rare but is life-threatening). I suggested the patient take these two drugs carefully. I told the man if he have the symptoms or signs of serotonin syndrome he should withdraw both drug immediately and back to hospital for further care if necessary.


The Neurology Clinics prescribled fluoxetine accompanied by mirtazapine  to a middle-age man. The dosage and frequency for fluoxetine is 20mg po Qd meanwhile that for mirtazapine is 30mg po Qd.

I checked these two drugs in drug interaction checker and a drug interaction was found between fluoxetine and mirtazapine – Fluoxetine and mirtazapine both increase serotonin levels, potential for dangerous interaction ( may causes serotonin syndrome, although serotonin is rare but life-threatening).

So due to this drug interaction, when I was dispensing these two to him, I asked him whether he was also taking or had recently taken any other psychotropic medications such as antidepressants, MAOIs, SSRIs or some drugs such as analgesics and so on, which also increase serotonin levels and may cause serotonin syndrome if they are coadministered. He told me negative. So I told him that he could take these two medications in combination, but should take with caution due to the drug interaction between fluoxetine and mirtazapine. And the most important is that I taught him how to identify serotonin syndrome. Simply that the general symptoms and signs of serotonin syndrome are clonus, agitation or diaphoresis, tremor and hyperreflexia or hypertonia, temperature above 100.4°F (38° C) and I said if he have any symptoms or signs of serotonin syndrome both drugs should be withdrawed immediately and he should go back to hospital for further care if necessary, I told him.

Finally the patient told me he knew what he should and took both drugs home.


Serotonin is a neurotransmitter that is synthesized from the amino acid L-tryptophan. Synthesis is necessary in the central and peripheral nervous system because serotonin cannot cross the blood-brain barrier. Once synthesized, serotonin is either stored in neuronal vesicles or metabolized by monoamine oxidase (MAO) to 5-hydroxyindoleacetic acid. Serotonin binds 1 of 7 postsynaptic 5-hydroxytryptophan (5-HT) receptors. The hyperstimulation of the 5-HT receptors in the brain and/or spinal cord is the cause of serotonin syndrome. So what is serotonin syndrome? Serotonin syndrome, characterized by mental status changes, neuromuscular dysfunction, and autonomic instability, is thought to be secondary to excessive serotonin activity in the spinal cord and brain. Serotonin syndrome is a potentially life-threatening set of symptoms caused by serotonin toxicity, and usually involves a combination of psychotropic medications that increase serotonergic transmission. That means specific drug interactions can be the reason for serotonin syndrome. Serotonin syndrome can ensue after the addition of a second serotonergic drug to an existing drug regimen or with administration of a serotonergic drug before allowing an inadequate washout period after discontinuation of another serotonergic drug. Potential mechanisms and corresponding agents of serotonin syndrome include:

  1. Increasing production of serotonin by providing increased amount of precursors – L-tryptophan-containing substances;
  2. Prevention of metabolism of stored serotonin – Monoamine oxidase inhibitors (MAOIs);
  3. Increased release of stored serotonin – Amphetamine, cocaine, fenfluramine, methylenedioxymethamphetamine (MDMA or ecstasy), or meperidine;
  4. Prevention of reuptake of serotonin released into the synapse – SSRIs, tricyclic antidepressants (TCAs), MDMA, dextromethorphan, meperidine, or St John’s Wort;
  5. Direct stimulation of serotonin receptors – Buspirone, lysergic acid, diethylamide (LSD);
  6. Unknown mechanism – Lithium.

I summarize the drugs which are implicated in serotonin syndrome. They are in  Table 1.



Amphetamines and their derivativesEcstasy Dextroamphetamine, Methamphetamine and Sibutramine
AnalgesicsCyclobenzaprine, Fentanyl, Meperidine, Tramadol
Antidepressants/Mood stabilizersBuspirone, Lithium
Monoamine Oxidase InhibitorsPhenelzine
Serotonin-Norepinephrine Reuptake InhibitorsVenlafaxine
Serotonin 2A Receptor BlockersTrazodone
St. John’s Wort
Tricyclic Antidepressants
AntiemeticsMetoclopramide, Ondansetron
Antimigraine Drugscarbamazepine, ergot alkaloids, triptans, and valproic acid

Table 1 Drugs that are potential to serotonin syndrome.

Other drugs if used in combination that may cause serotonin syndrome include cocaine, dextromethorphan, linezolid, l-tryptophan, and 5-hydroxytryptophan. (more…)

Maternal Antidepressant Use May Promote Pregnancy-Induced Hypertension

July 19, 2012 Adverse Drug Reactions, Pregnancy Medicine 2 comments , , , , ,

Today I read an article that disscusses the adverse effects of the antidepresants use during pregnancy. It says that when using antidepressant during pregnancy will causes hyperstension. The article is below.

One thing I want to emphase is that according to the authors of this study in the article, 4% to 14% of pregnant women are receiving antidepressants. Indeed, depression is one of the most commmon chronic illnesses among pregnant women. But should we use antidepressants during pregnancy? I check one of  antidepresants – Paroxetine – one of the SSRIs on medscape. Paroxetine belongs to Pregnancy Category: D and has Teratogenic Effects: Paroxetine increases the risk of congenital malformations, particularly cardiovascular malformations.

As above I think pregnancy should be one of the contraindications of this SSRI due to the teratogenic effects. Maybe all SSRIs have the effect of teratogenicity during pregnancy, but 4% to 14% of pregnant women are receiving antidepressants, maybe also the SSRIs such as Paroxetine. So anyone can tell me in U.S. do the pregnant women receive SSRIs to treat depression?

Clinical Context

Depression is one of the most common chronic illnesses among pregnant women, with a prevalence of approximately 20%. According to the authors of the current study, 4% to 14% of pregnant women receive antidepressants, and these medications are not without adverse effects. The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy is most associated with a modest increase in the risk for congenital abnormalities, including heart defects.

Less data suggest serious adverse events of antidepressants on the pregnancy itself. However, antidepressants generally increase levels of circulating serotonin, which can, in turn, raise blood pressure. Some previous research has suggested that antidepressants can increase the risk for pregnancy-induced hypertension and preeclampsia during pregnancy. The current study by De Vera and Bérard uses a large patient database to further investigate the association between pregnancy-induced hypertension and antidepressants.

Study Synopsis and Perspective

Women who use antidepressants while pregnant have an increased risk of developing pregnancy-induced hypertension, new research shows.

The increased risk is beyond the risk that could be attributed to their depression or anxiety disorders, Mary A. De Vera, PhD, from the University of Montreal, and Anick Bérard, PhD, from Sainte Justine Research Center, Montreal, Quebec, Canada, write.

“Antidepressants are used widely during pregnancy, up to 14% of pregnant women use them,” Dr. Bérard told Medscape Medical News. “Our study adds one more piece to the puzzle with regard to the risk of using antidepressants during pregnancy.”

The study is published online March 22 in the British Journal of Clinical Pharmacology.

Do Not Stop Meds

SSRIs are the main antidepressants in use today, and serotonin is a vasoconstrictor and also directly affects diastolic blood pressure, although the mechanism of action for this is not very well understood, Dr. Bérard noted.

In this study, the researchers analyzed data from the Quebec Pregnancy Registry and compared 1216 women who had been diagnosed with pregnancy-induced hypertension, with or without preeclampsia, who had no history of hypertension before they became pregnant, with 12,160 matched control individuals.

They found that among the participants with pregnancy-induced hypertension, 45 (3.7%) had used antidepressants during pregnancy, compared with 300 (2.5%) of the women in the control group (odds ratio [OR], 1.52; 95% confidence interval [CI] 1.10 – 2.09).

Antidepressant use during pregnancy was associated with a 53% increased risk for pregnancy-induced hypertension (OR, 1.53; 95% CI, 1.01 – 2.33). Use of SSRIs was associated with a 60% increased risk (OR, 1.60; 95% CI, 1.00 – 2.55); of the SSRIs, paroxetine was associated with the greatest risk for pregnancy-induced hypertension (OR, 1.81; 95% CI, 1.02 – 3.23).

“It is very important for physicians and women to discuss the risks and benefits of antidepressants before prescribing,” said Dr. Bérard.

“Close monitoring needs to be done, because there could be benefits, and there can also be risks. The message isn’t as simple as telling pregnant women to stop taking antidepressants.

“The decision has to be made one woman at a time. Anyone affected by this study should not stop taking their prescribed medication but seek a consultation with their doctor if they are concerned,” she said.

“Important” Limitations

Linda Chaudron, MD, associate chair for clinical services in the Department of Psychiatry at the University of Rochester Medical Center in New York, said the study adds to recent studies that have explored the hypothesis of an association between antidepressant use and pregnancy-induced hypertension. (more…)