A COMMON PATHOGENESIS OF THE SEROTONIN SYNDROME, CATATONIA, AND NMS
To the Editor:
A recent article in Psychiatric Annals on the serotonin syndrome intrigued us because it demonstrated the clinical overlap of the serotonin syndrome with the neuroleptic malignant syndrome (NMS).1 These two disorders, together with catatonia, have many clinical similarities (ie, cognitive, behavioral, neuromuscular, and autonomic nervous system dysfunction with variable hyperthermia). Experts in the field of NMS have conceptualized NMS as a severe variant of the catatonic syndrome.2 Serotonin syndrome is part of the differential diagnosis of NMS due to signs and symptoms.
The pathogenesis of serotonin syndrome is reported to be due to serotonin hyperactivity at the 5-HT1A receptor.3 The 5-HT1A receptor is believed to mediate anxiety and mood effects, but may have other effects as well. Furthermore, recent studies have indicated that there are at least 14 subtypes on the serotonin receptor, suggesting that additional 5HT receptors may also mediate serotonin syndrome.4
One proposed model of catatonia and NMS incorporates 5HT^sub IA^ receptor hyperactivity.5 In this model, catatonia and NMS are considered a single entity that results from variable combinations of the following: (1) GABA hypoactivity at the GABAa receptor; (2) dopamine hypoactivity at the D2 receptor; (3) serotonin hyperactivity at the 5-HT^sub 1A^ receptor and hypoactivity at the 5-HT^sub 2A^ receptor; and (4) glutamate hypoactivity at the NMDA receptor.
Myoclonus, which presents commonly in the serotonin syndrome but infrequently in catatonia and NMS, has been used as a distmguishing diagnostic feature. The GABAa receptor appears to be the primary mediator of myoclonus, in concert with other neurochemical systems.6 Recent animal models of myoclonus indicate that 5-HT1 A activity may be influential in GABA hypoactivity.
Although the treatment approaches for serotonin syndrome are prelirninary, there is some overlap in the treatment approaches for serotonin syndrome, NMS, and catatonia. These syndromes appear to be time limited in most cases, with supportive treatment being an important factor in their outcomes.
We recommend that serotonin syndrome, NMS, and catatonia be considered allied conditions based on the commonality of the proposed 5-HT^sub 1A^ hyperactivity in their pathogenesis. In addition, we recommend further research into the role of the serotonin system in these disorders.
1. Keck PE, Arnold LM. The serotonin syndrome. Psychiatric Annals. 2000; 30:333-343.
2. Fricchione G, Mann SC, Caroff SN. Catatonia, lethal catatonia, and neuroleptic malignant syndrome. Psychiatric Annals. 2000;30:347-355.
3. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705713.
4. Cryan JF, Leonard BE. 5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response. Human Psydiopharmacobgy: Clinical and Experimental. 2000;15:113-135.
5. Carroll BT. The universal field hypothesis of catatonia and neuroleptic malignant syndrome. CNS Spectrums. 2000;26-33.
6. Matsumoto RR, Truong DD, Nguyen KD, et al. Involvement of GABA(A) receptors in myoclonus. Mov Disord. 2000;15:47-52.