Did Internet-Purchased Diet Pills Cause Serotonin Syndrome? Phentermine Also May Have Increased Patient's Neuroleptic Malignant Syndrome Risk

By Bin Im, Kyoung; Fiedorowicz, Jess G. | Current Psychiatry, July 2008 | Go to article overview

Did Internet-Purchased Diet Pills Cause Serotonin Syndrome? Phentermine Also May Have Increased Patient's Neuroleptic Malignant Syndrome Risk


Bin Im, Kyoung, Fiedorowicz, Jess G., Current Psychiatry


Ms. G, age 28, presents to a tertiary care hospital with altered mental status. Six weeks ago she started taking phentermine, 37.5 mg/d, to lose weight. Her body mass index is 24 kg/[m.sup.2] (normal range), and she obtained the stimulant agent via the Internet. Her family reports Ms. G was very busy in the past week, staying up until 2 AM cleaning. They say she also was irritable with her 5-year-old son.

[ILLUSTRATION OMITTED]

Two days ago, Ms. G complained of fatigue and nausea without emesis. She went to bed early and did not awaken the next morning. Her sister found her in bed, minimally responsive to verbal stimuli, and brought her to the hospital.

Patients have used phentermine as a weight-reducing agent since the FDA approved this amphetamine-like compound in 1960.(1) Phentermine's mechanism of action is thought to involve dopaminergic, noradrenergic, and serotonergic effects.(2) Stimulation of norepinephrine (NE) release is its most potent effect, followed by NE reuptake inhibition, stimulation of dopamine (DA) release, DA reuptake inhibition, stimulation of serotonin (5-HT) release, and 5-HT reuptake inhibition (weak). (3)

Because phentermine could in theory cause serotonin syndrome, (4) its use is contraindicated with monoamine oxidase inhibitors (MAOIs) and not recommended with selective serotonin reuptake inhibitors (SSRIs).(5) One case report describes an interaction between fluoxetine and phentermine that appears consistent with serotonin syndrome.(6) We are aware of no case reports of serotonin syndrome caused by phentermine alone.

This article reports the case of Ms. G, who presented with probable serotonin syndrome associated with phentermine use and subsequently developed a rapidonset, superimposed neuroleptic malignant syndrome (NMS). We hypothesize that phentermine use may increase NMS risk through adverse drug events and discuss potential pathophysiologic mechanisms and treatment implications.

Serotonin syndrome vs NMS

Serotonin syndrome is an infrequent and potentially life-threatening adverse drug reaction that presumably results from excess serotonin activity (Box 1).(7-10) NMS also is an infrequent and potentially life-threatening neurologic emergency (Box 2, page 70). (11-18) Similarities between disorders of increased serotonergic activity and disorders of low dopaminergic activity (Table 1) suggest both may result from an imbalance between the serotonergic and dopaminergic systems, which have reciprocal relationships in the CNS.(19)

Table 1
Signs and symptoms of NMS vs serotonin syndrome

                  NMS                        Serotonin syndrome

Onset             Insidious, days to weeks   Acute (minutes to
                                             hours)

Resolution        Slow, often > 1 week       Improvement or resolution
                                             Often within 24 hours.

Autonomic         Fever, tachycardia,        Diaphoresis, shivering,
                  diaphoresis, elevated      tachycardia,
                  or labile blood            hypertension, mydriasis
                  pressure, sialorrhea,
                  tachypnea, incontinence

Gastrointestinal  Dysphagia, elevated        Diarrhea, nausea,
                  Transaminases              vomiting, elevated
                                             ammonia and
                                             transaminases

Neuromuscular     Rigidity, bradykinesia,    Clonus, myoclonus,
                  dysarthria, dyskinesias,   hyperreflexia,
                  coarse tremor, ataxia,     ataxia,
                  opisthotonos, oculogyric   incoordination,
                  crisis, rhabdomyolysis     rigidity, tremor

Psychiatric       Altered mental status,     Altered mental
                  stupor, somnolence,        status, agitation,
                  mutism                     hypomania,
                                             hyperactivity,
                                             restlessness,
                                             somnolence (less
                                             common)

Other             Leukocytosis, elevated     Leukocytosis
                  creatine kinase            (rarely > 20K
                  (significant), elevated    cells/m[m. … 

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