OBJECTIVES: PBA is a neurologic disorder characterized by involuntary, uncontrollable laughing and/or crying episodes that are often incongruent with the patient’s internal emotional state; PBA has also been called pathological laughing/crying, emotionalism, etc. Until FDA approval of dextromethorphan/quinidine (DM/Q) in 2010, multiple agents including antidepressants, antipsychotics, dopamine agonists and sedatives were used off-label for the management of PBA symptoms. We conducted a systematic review of therapies (licensed and unlicensed) for PBA symptoms to evaluate their relative clinical effectiveness METHODS: Databases: Medline, Medline in process, Embase and the Cochrane central register of controlled trials; conference abstracts were searched in Embase. Study type: RCTs and non-RCTs in adult patients with PBA/PBA-like symptoms (pathological laughing/crying, emotionalism, etc). Interventions: DM/Q, antidepressants, antipsychotics, dextromethorphan and quinidine alone. Outcome measures: change from baseline in various measures of PBA/emotionalism symptoms or symptom burden (NPI, SF-36, PRS scores and the caregiver strain index (CSI)). RESULTS: Nine RCTs and three observational studies were included. Among off-label drugs, six RCTs of 3 SSRIs and 2 TCAs showed improvements in disparate PBA  symptom measures,  only 1 used a validated symptom measure. These studies were small (N=6-28) using mostly stroke patients. They were heterogeneous on how they defined/diagnosed PBA and varied in duration (1.4-24 weeks). As such, no formal evidence synthesis was possible.  Three RCTs and one open label trial investigating DM/Q included a well-defined and diverse PBA patient population, showing statistically significant improvements in a range of validated clinical and HRQoL outcomes relevant for the treatment of PBA. CONCLUSIONS: The evidence base for off-label agents used for treatment of PBA is limited, relying on small often uncontrolled studies showing ill-defined treatment effects and little or no safety tracking. DM/Q is the only treatment for PBA that has demonstrated efficacy in well-conducted clinical trials in patients with varied neurological disorders.