Pharmacotherapy for the Pseudobulbar Affect in Individuals Who Have Sustained a Traumatic Brain Injury: a Systematic Review

  • Amelia J. HicksEmail author
  • Fiona J. Clay
  • Jennie L. Ponsford
  • Luke A. Perry
  • Mahesh Jayaram
  • Rachel Batty
  • Malcolm Hopwood


Pseudobulbar affect is a debilitating condition that significantly reduces quality of life for many individuals following traumatic brain injury (TBI). It is characterized by embarrassing and often uncontrollable episodes of crying or laughter. The aim of this systematic review was to evaluate the effectiveness of pharmacotherapy as compared to all other comparators for the management of pseudobulbar affect in adults who have sustained TBI. Six databases were searched, with additional hand searching of journals, clinical trials registries and international drug regulators to identify published and unpublished studies in English up to June 2018. Studies were eligible for this review if they included adults who had sustained a medically confirmed TBI and presented with pseudobulbar affect. All pharmacotherapy and comparator interventions were considered for inclusion, and study design was not limited to randomised controlled trials. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Two quasi-experimental studies examining the effectiveness of dextrometamorphan/quinidine (DM/Q) were identified. These studies reported that DM/Q was effective in reducing symptoms of pseudobulbar affect and had a positive safety profile, over follow-up periods of 3 months (n = 87) and 12 months (n = 23). However, both studies were limited by lack of a control group and a high dropout rate. The findings of twelve case reports examining the effectiveness of DM/Q (n = 6) and anti-depressants (n = 6) are also discussed. Further research is required to determine which pharmacological interventions provide the best outcomes for individuals with pseudobulbar affect following TBI, with consideration given to side effect profiles and financial costs.


Pseudobulbar affect Traumatic brain injury TBI Pharmacotherapy Effectiveness 



computed tomography


Center for Neurologic studies Emotional Lability Scale








Glasgow Coma Scale


head injury




Joanna Briggs Institute


magnetic resonance imaging




not reported


not applicable


pseudobulbar affect


Pathological Laughter and Crying Scale


pro re nata (i.e. as needed)


post traumatic amnesia


Risk of Bias


selective serotonin reuptake inhibitor


traumatic brain injury


tricyclic anti-depressant







The authors acknowledge with thanks the input of our information specialist Farhad Shokraneh in the design of search strategies.

Funding Information

The project was funded by the Transport Accident Commission (TAC) through the Institute for Safety, Compensation and Recovery Research (ISCRR).The funder was not involved in any other aspect of the project. This includes study design, data collection, analysis and interpretation of data, writing of the report or decision to submit the article for publication.

Compliance with Ethical Standards

Conflict of Interest

One of the chief investigators (MH) has given talks on this topic for which travel and accommodation has been paid by the organizers. In addition, he has accepted fees for consulting and research from the pharmaceutical companies Bionomics, Eli Lilly, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Praxisand Servier. Lundbeck. All other authors declare no known competing interests.

Supplementary material

11065_2020_9427_MOESM1_ESM.docx (43 kb)
ESM 1 (DOCX 42 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Monash-Epworth Rehabilitation Research Centre, Turner Institute for Brain and Mental Health, School of Psychological SciencesMonash UniversityMelbourneAustralia
  2. 2.Department of PsychiatryUniversity of MelbourneMelbourneAustralia
  3. 3.Department of Forensic MedicineMonash UniversitySouthbankAustralia
  4. 4.Albert Road Clinic, Department of PsychiatryUniversity of MelbourneMelbourneAustralia

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