Page 106 - JCBP-3-1

Journal of Clinical and
Basic Psychosomatics Serotonin syndrome unexpected medication

the absence of nystagmus, clonus, jerkiness, tremors, or no adverse effects recurred, proving it less likely to be the
akathisia. Furthermore, the mental status examination primary cause of our patient’s complaints. Phentermine
demonstrated considerable improvement, as evidenced may have affected this patient’s serotonin levels; however,
by the return to baseline attention without agitation. no evidence of serotonin syndrome occurring with
9
Cyproheptadine was discontinued, and duloxetine was phentermine administration currently exists. This does
resumed at a dose of 30 mg on day 5. The patient continued exclude a theoretical mechanism, but phentermine is
to improve clinically and was discharged on day 6. unlikely to be the primary offending agent. Given the
patients’ long-term compliance with bupropion before
3. Discussion symptoms appeared, it is also unlikely to be the cause of the
Serotonin syndrome is a potentially fatal condition resulting symptoms. To our knowledge, there are only three reported
from excessive serotonergic activity. It is characterized cases demonstrating serotonin syndrome in conjunction
by somatic, autonomic, and cognitive symptoms, with bupropion toxicity, and none of these were caused
19
including altered mental status, autonomic instability, and by bupropion alone. Finally, on the Naranjo Adverse
neuromuscular anomalies. Although frequently linked Drug Reaction Probability Scale, our patient scored an 8,
to MAOIs, SSRIs, and SNRIs, other agents, including making metaxalones a “probable” cause of the medication
20
muscle relaxants and weight reduction pills, have also been reaction (Figure 1). This case report emphasizes that
associated with its development. understanding pharmacodynamic interactions is crucial,
particularly in serotonergic polypharmacy.
The patient in the current case was receiving several
medications that affect serotonin levels through diverse It is essential that clinicians understand drug serotonergic
mechanisms. Duloxetine, an SNRI, increases serotonin potential. Medications not traditionally associated with
and norepinephrine levels by inhibiting their reuptake. serotonin syndrome, such as metaxalone or weight loss drugs,
10
Bupropion, primarily an NDRI with certain serotonergic can still cause serotonin syndrome when coupled with other
effects, is a known risk factor. Phentermine, a serotonergic drugs. Drug-drug interactions must be carefully
11
sympathomimetic amine used for weight loss, can indirectly considered when prescribing multiple neurotransmitter-
21
enhance serotonin’s release. Although metaxalone is a affecting medications. Early diagnosis of serotonin
12
muscle relaxant and its exact mechanism of action is not syndrome is crucial to prevent severe complications and
fully understood, it appears to have serotonergic properties improve outcomes. Management involves prompt cessation of
that, when combined with other serotonergic agents, can all serotonergic agents and supportive care. Benzodiazepines
cause serotonin syndrome. Increasing evidence suggests are considered first-line drugs; serotonin antagonists such as
6
that the mechanism of action of metaxalone comprises cyproheptadine are reserved for severe cases in which there is
22
MAOI activity that becomes clinically relevant when given minimal improvement with benzodiazepines.
in large doses. In addition, hepatic cytochrome P450 The patient’s symptomatology was consistent with
5,13
enzymes facilitate metaxalone metabolism. Specifically, that of serotonin syndrome, as evidenced by his agitation,
CYP1A2 and CYP2D6 have been demonstrated to be altered mental status, hyperreflexia, clonus, and autonomic
the primary enzymes responsible for metabolism. Our
14
patient was receiving both duloxetine and bupropion,
which are known CYP2D6 inhibitors. 15,16 Furthermore,
17
duloxetine inhibits CYP1A2. Even at therapeutic
levels, this combination may have resulted in increased
bioavailability of metaxalone, making its MAOI activity
clinically relevant. We believe that these medications likely
caused excess neurological serotonin formation, leading to
dysregulation and patient’s clinical manifestations.
One limitation of this case report was the other
serotoninergic agents that the patient was concurrently
receiving, specifically duloxetine, phentermine, and to
some extent bupropion. Duloxetine is associated with
serotonin syndrome; however, its incidence is low, and the
time course of symptom onset appears to be more closely
related to the use of metaxalone on an as-needed basis. In Figure 1. Naranjo Adverse Drug Reaction Probability Scale. Modified
18
addition, after resuming duloxetine during hospitalization, from Naranjo et al. 20

Volume 3 Issue 1 (2025) 100 doi: 10.36922/jcbp.4490