Phentermine is an anorexigen which had been approved for short-term use as a treatment of obesity by US FDA in 1959, and has been used since. Phentermine stimulates the secretion of noradrenalin in the central nervous system, and suppresses appetite by regulatingthe β-adrenergic receptors.11
When phentermine and fenfluramine combination treatment was reported to have a synergistic effect on the dopamine and serotonin release in the rat brain,10
Fen-Phen treatment became the mainstay of anorexin treatment of the 1980s. However, this combination treatment was suggested to have strong ties with PAH and valvular heart disease while fenfluramine single medication was also reported with the same side-effects that in November 1997 the US FDA banned the prescription of fenfluramine altogether. However, to date, the FDA still allows the short term use of phentermine. In the 2000 report by Rich, et al.,12
concerning the surveillance data on anorexigens and pulmonary hypertension, the only drug that had a meaningfully causal relationship with PPH amongst antidepressants, anorexigens, and amphetamines was fenfluramines. So far, there exists very few cases and no controlled studies suggesting a connection between PPH and the use of other appetite suppressants such as phentermine.13,14
A concrete evaluation on the safety of phentermine single treatment is still unavailable and there has not been a reported case since 2000.15
However, there had been studies in the 1990s that raised suspicions that phentermine might have similar correlations with PAH as with fenfluramine. In one study, fenfluramine-like medications were suggested to increase the risk of PPH via affecting serotonin [5-Hydroxytryptamine (5-HT)] transporters.16
Rothman, et al.17
reported that some medications known to increase the risk of PPH (e.g., aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter substrates. The role of 5-HT transporters in the development of PAH has been well-evaluated. 5-HT transporter substrates are translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic toxicity, and individual susceptibility, PPH may develop as a response to concentrations of these drugs or metabolites. According to Rothman, the duration and dosage of the drug also had a direct relationship with the increase in the relative risk of PAH after treatment. If this evidence can be supported by a considerable number of clinical cases, the FDA must amend its decision to allow the usage of a drug that is now in use without safe guidelines. The current Physician's Desk Reference (PDR) guideline allows phentermine for a duration of 3-6 weeks; however, in our case, the patient had developed PAH with 5 weeks of medication.
In summary, we propose that the usage of phentermine might be associated with PAH by presenting the above case. Although phentermine has been considered a safe drug for obesity, further study should be underway to establish safety and dosage of phentermine.