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High-Dose Methylphenidate Use Prior to Hospitalization Exacerbates the Withdrawal Syndrome in Inpatients Treated for Opioid and Sedative-Hypnotic Co-Dependence - Case Series and Review of the Literature.

Methylphenidate (MPD) is a psychostimulant with dopamine and noradrenaline reuptake inhibition characteristics, frequently prescribed for treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD). Synthesized in 1944, and subsequently marketed in 1954, it was initially used for treatment of hypotension, narcolepsy and sedative-induced coma. From the 1960ies, it has been prescribed for the treatment of ADHD, and this is most common indication of the drug, even not without controversy. Presently, it is among the fifty most prescribed medications in the USA, but less so in other countries. Similar to other stimulant psychotropic drugs, the abuse of MPD is common (Bjarnadottir et al. 2016), especially among students, long-distance drivers and in people with substance use disorder. Acutely, mixing psychostimulants and central nervous system depressants can lead to initial euphoria, which can give way to subsequent overdose due to continual upping of doses of CNS-depressants whose effects are not readily felt, but overshadowed by the intensive effects of stimulants. In the long run, users may self-medicate psychostimulant withdrawal symptoms with CNS-depressants and vice versa. Stimulant/ depressant co-dependence can influence withdrawal length or severity. The most investigated co-dependence of this type is cocaine/alcohol co-dependence. Cocaine co-dependence was not found to affect intensity of alcohol withdrawal symptoms (Kampman et al. 2002). Among cocaine/alcohol co-dependent subjects, cocaine use severity seems a better predictor of a successful detoxification than alcohol use severity (Kampman et al. 2004). In cocaine users on maintenance opioid therapy, a two component model was noticed: cocaine use was found to provoke opioid withdrawal-like symptoms in subjects on high maintenance opioid doses (e.g. 6 mg of buprenorphine or 120 mg of methadone) but had no effect on subjects receiving low-dose opioid maintenance therapy (Stine & Kosten 1994). Sedative-hypnotics were found to influence the abuse potential of other drugs through direct and indirect actions on hypothalamic pituitary adrenal axis and the mesocorticolimbic system (Schelp et al. 2018). The impairing effects during everyday activities, like driving, were found more prominent in amphetamines/benzodiazepines co-dependent subjects that in those who