Letters to the Editor Effective treatment of narcolepsy–cataplexy with duloxetine: A report of three cases To the Editor: We conducted a pilot study on duloxetine, a new nor- epinephrine and serotonin reuptake inhibitor (SNRI) [1], in the treatment of narcolepsy–cataplexy. Several major drug classes, including aminergic reuptake inhib- itors, improve cataplexy in patients with narcolepsy [2]. Since the SNRI venlafaxine may be effective for cata- plexy, we utilised the more balanced and potent SNRI duloxetine [1]. We selected three patients (1 F and 2 M, aged 22–64) suffering from narcolepsy–cataplexy, diagnosed accord- ing to ICSD-2 [3]. They suffered from excessive daytime somnolence (EDS) and cataplexy involving lower limbs and/or the jaw, triggered by anger or laughter (weekly frequency). A single morning dose of duloxetine 60 mg, in addition to modafinil 200 mg b.i.d, induced in the first patient a dramatic decrease of cataplexy and EDS reduction within the first week. Duloxetine as monotherapy led to cataplexy remission and EDS improvement in the remaining two. Polysomnography, the multiple sleep latency test, Epworth sleepiness scale (ESS) score, and cataplexy frequency are summarized in Table 1 (at baseline and after a six month follow- up). No tolerance phenomenon or adverse events were evident after one year follow-up. To our knowledge these are the first cases of nar- colepsy–cataplexy responsive to duloxetine. Our find- ings (REM sleep suppression, REM sleep latency increase and ESS improvement) are supported by re- cent studies reporting REM sleep suppression and REM sleep latency increase induced by duloxetine in depressed patients [4] as well as in healthy subjects [5]. The two patients treated with monotherapy showed a mild reduction of the comorbid severe PLMI after duloxetine; however, this finding may be merely due to the variability from night to night of PLMI [6]. Unlike most antidepressants [3], toler- ance or adverse events did not occur after one year follow-up, confirming a long term efficacy for cata- plexy and EDS. The above cases suggest a rapid and powerful anti- cataplectic activity of duloxetine, strongly associated with EDS improvement in narcolepsy. If consistently replicated in a larger cohort with a placebo-controlled design, duloxetine efficacy for narcolepsy–cataplexy may represent a new therapeutic option for this dis- abling disorder. Table 1 PSG, MSLT, ESS, and clinical features at baseline (T0) and after 6 months of stable treatment with duloxetine (T1) PSG MSLT ESS score Cataplexy frequency (n/month) SE (%) REM latency REM % PLMI SOL min SOREMP (n) T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 1 38.1 89.3 1.5 275 35 16.6 79.2 56.4 2 9.37 3 2 21 12 30 1 2 81.7 83 5 55.5 17.9 12.5 0 0 5.5 11.5 3 0 11 5 4 0 3 73.4 89 100 120 10 8 56.3 37.4 8 13.5 0 0 14 3 12 0 Definitions. PSG, nocturnal polysomnography; MSLT, multiple sleep latency test; SE, Sleep efficiency. SE is defined as the total sleep time per time in bed; REM sleep is expressed as percentage of total sleep time; PLMI, periodic limb movements index for hour; SOL, mean sleep onset latency; SOREMP, sleep onset REM period. ESS score, Epworth Sleepiness Scale score. www.elsevier.com/locate/sleep Sleep Medicine 10 (2009) 153–155