The evidence for the hypothesis that dopamine blockade is central to neuroleptic malignant syndrome (NMS) is mostly circumstantial, but is related to the fact that NMS is precipitated by antipsychotics that block dopamine receptors. Dopamine receptors in the hypothalamus are integral to the regulation of body temperature and their blockade results in hyperthermia and autonomic instability. The patient with NMS classically develops worsening altered mental status over the course of several days after, or during, treatment with an antipsychotic medication. The most important aspect of treatment for NMS is the discontinuation of the offending medication (or restarting a previously held dopamine agonist) followed by supportive care. Benzodiazepines should be used as a component of supportive care in patients with increased sympathetic tone. Dopamine agonists such as bromocriptine and amantadine have been advocated as possible therapies based on a theory that NMS is primarily caused by dopamine blockade.

Fibromyalgia is marked by high interpatient variability in both clinical course and efficacy of particular therapies. Fibromyalgia pain does not result from peripheral nociceptor stimulation but instead arises from deficient CNS processing and modulation of pain signals. Tricyclic antidepressants (TCAs) and related drugs have some efficacy when compared with placebo in clinical trials. In addition to TCAs and antidepressants, the other commonly seen approach to treating fibromyalgia pain is the use of anticonvulsants. In fibromyalgia patients taking long-term opioids, a methodologically rigorous study shows that administration of the non-ergot dopamine agonist pramipexole significantly reduces pain and improves myriad quality-of-life indices. The benzodiazepines are also associated with mixed results in fibromyalgia trials. Given the lack of inflammatory pathophysiology in fibromyalgia, it is not surprising that no data support use of corticosteroids or NSAIDs in treating fibromyalgia pain.