Skip to main content

Drug-Induced Intracranial Hypertension: A Systematic Review and Critical Assessment of Drug-Induced Causes



Idiopathic intracranial hypertension (IIH) is a condition with increased intracranial pressure of unknown etiology. Its presenting symptoms include persistent headache, pulsatile tinnitus, and visual obscuration. It tends to occur in obese women of childbearing age, and its greatest risk is irreversible loss of vision. Some of the commonly used medications in dermatology, especially those for acne vulgaris, have been associated with IIH. However, the creation of specific risk categories for drugs as a guide for clinicians has never been performed.


The aim of this study was to critically assess all published cases of IIH and identify high-risk drugs associated with drug-induced intracranial hypertension (DIIH), to assist dermatologists and other physicians with patient education and monitoring of symptoms of secondary intracranial hypertension.


MEDLINE, EMBASE, and Cochrane Review Databases were searched for all cases of IIH thought to be drug-related between January 1900 and June 2019. A total of 5117 articles were identified, and 235 articles were found to be relevant. All cases were assessed to satisfy the modified Dandy criteria for diagnosis of IIH, and the likelihood of each case being a ‘definite’ adverse drug reaction (ADR) was determined using the Koh algorithm for ADR. An association category (from weakly associated [Category I] to strongly associated [Category V]) was assigned based on the number of cases meeting these two criteria.


There were 259 verifiable cases of DIIH. Vitamin A derivatives, tetracycline-class antibiotics, recombinant growth hormone, and lithium were found to be most strongly associated with DIIH (Categories IV and V). Corticosteroids were moderately associated with DIIH (Category III). Drugs that were weakly associated with DIIH (Categories I and II) include cyclosporine, progestin-only contraceptives, combined oral contraceptives, second- and third-generation fluoroquinolones, sulfenazone, gonadotropin-releasing hormones and luteinizing hormone-releasing hormone agonist, nalidixic acid, amiodarone, stanozolol, danazol, divalproic acid, sulfasalazine, ketoconazole, and ustekinumab.


We suggest using the term ‘drug-induced intracranial hypertension’ (DIIH) and propose a set of diagnostic criteria for DIIH. Our review attempts to identify DIIH-associated drugs based on a strict diagnostic and drug-causality algorithm, then stratify them into appropriate risks categories. This may ultimately assist physicians in counselling patients about the risk of DIIH when prescribing medications and recognizing this uncommon yet sight-threatening condition.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81:1159–65.

    Article  Google Scholar 

  2. 2.

    Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol. 2005;6:29–37.

    Article  Google Scholar 

  3. 3.

    Koh Y, Yap CW, Li SC. A quantitative approach of using genetic algorithm in designing a probability scoring system of an adverse drug reaction assessment system. Int J Med Informatics. 2008;77:421–30.

    Article  Google Scholar 

  4. 4.

    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

  5. 5.

    Kushida A, Tamura H. Retinoic acids induce neurosteroid biosynthesis in human glial GI-1 Cells via the induction of steroidogenic genes. J Biochem. 2009;146:917–23.

    CAS  Article  Google Scholar 

  6. 6.

    Warner JE, Bernstein PS, Yemelyanov A, Alder SC, Farnsworth ST, Digre KB. Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension. Ann Neurol. 2002;52:647–50.

    CAS  Article  Google Scholar 

  7. 7.

    Lombaert A, Carton H. Benign intracranial hypertension due to A-hypervitaminosis in adults and adolescents. Eur Neurol. 1976;14:340–50.

    CAS  Article  Google Scholar 

  8. 8.

    Spector RH, Carlisle J. Pseudotumor cerebri caused by a synthetic vitamin A preparation. Neurology. 1984;34:1509–11.

    CAS  Article  Google Scholar 

  9. 9.

    Fraunfelder FW, Fraunfelder FT, Corbett JJ. Isotretinoin-associated intracranial hypertension. Ophthalmology. 2004;111:1248–50.

    Article  Google Scholar 

  10. 10.

    Lee AG. Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. Cutis. 1995;55:165–73.

    CAS  PubMed  Google Scholar 

  11. 11.

    Fraunfelder FT, LaBraico JM, Meyer SM. Adverse ocular reactions possibly associated with isotretinoin. Am J Ophthalmol. 1985;100:534–7.

    CAS  Article  Google Scholar 

  12. 12.

    Caruana DM, Wylie G. ‘Washout’ period for oral tetracycline antibiotics prior to systemic isotretinoin. Br J Dermatol. 2016;174:929–30.

    CAS  Article  Google Scholar 

  13. 13.

    Chiu AM, Chuenkongkaew WL, Cornblath WT, Trobe JD, Digre KB, Dotan SA, et al. Minocycline treatment and pseudotumor cerebri syndrome. Am J Ophthalmol. 1998;126:116–21.

    CAS  Article  Google Scholar 

  14. 14.

    Tintle SJ, Harper JC, Webster GF, Kim GK, Thiboutot DM. Safe Use of Therapeutic-Dose Oral Isotretinoin in Patients With a History of Pseudotumor Cerebri. JAMA Dermatol. 2016;152:582–4.

    Article  Google Scholar 

  15. 15.

    Jonnalagadda J, Saito E, Kafantaris V. Lithium, minocycline, and pseudotumor cerebri. J Am Acad Child Adolesc Psychiatry. 2005;44:209.

    Article  Google Scholar 

  16. 16.

    Caruana D, Wylie G. “Wash-out” period for oral tetracycline antibiotics prior to systemic isotretinoin. Br J Dermatol. 2015;173:34–5.

    Google Scholar 

  17. 17.

    Bettoli V, Borghi A, Mantovani L, Scorrano R, Minghetti S, Toni G, et al. Safe use of oral isotretinoin after pseudotumor cerebri due to minocycline. Eur J Dermatol. 2011;21:1024–5.

    CAS  Article  Google Scholar 

  18. 18.

    Law C, Yau GL, ten Hove M. Delayed development of intracranial hypertension after discontinuation of tetracycline treatment for acne vulgaris. J Neuroophthalmol. 2016;36:67–9.

    Article  Google Scholar 

  19. 19.

    Friedman DI, Gordon LK, Egan RA, Jacobson DM, Pomeranz H, Harrison AR, et al. Doxycycline and intracranial hypertension. Neurology. 2004;62:2297–9.

    CAS  Article  Google Scholar 

  20. 20.

    Levine A, Watemberg N, Hager H, Bujanover Y, Ballin A, Lerman-Sagie T. Benign intracranial hypertension associated with budesonide treatment in children with Crohn’s disease. J Child Neurol. 2001;16:458–61.

    CAS  Article  Google Scholar 

  21. 21.

    Chebli JM, Gaburri PD, de Souza AF, da Silva CE, Pinto JR, Felga GE. Benign intracranial hypertension during corticosteroid therapy for idiopathic ulcerative colitis: another indication for cyclosporine? J Clin Gastroenterol. 2004;38:827–8.

    Article  Google Scholar 

  22. 22.

    Bohm R, Hocker J, Cascorbi I, Herdegen T. OpenVigil-free eyeballs on AERS pharmacovigilance data. Nat Biotechnol. 2012;30:137–8.

    Article  Google Scholar 

  23. 23.

    Etminan M. Risk of intracranial hypertension with intrauterine levonorgestrel: reply. Ther Adv Drug Saf. 2016;7:25–6.

    CAS  Article  Google Scholar 

  24. 24.

    Rai R, Kirk B, Sanders J, Valenzuela R, Sundar S, Warner J, et al. The relationship between the levonorgestrel-releasing intrauterine system and idiopathic intracranial hypertension. Invest Ophthalmol Vis Sci. 2015;56:2228.

    Google Scholar 

  25. 25.

    Koerner JC, Friedman DI. Inpatient and emergency service utilization in patients with idiopathic intracranial hypertension. J Neuroophthalmol. 2014;34:229–32.

    Article  Google Scholar 

  26. 26.

    Ireland B, Corbett JJ, Wallace RB. The search for causes of idiopathic intracranial hypertension. A preliminary case-control study. Arch Neurol. 1990;47:315–20.

  27. 27.

    Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology. 1991;41:239–44.

    CAS  Article  Google Scholar 

  28. 28.

    Wall M. Idiopathic Intracranial Hypertension. Neurol Clin. 2010;28:593–617.

    Article  Google Scholar 

  29. 29.

    Reddy AR, Backhouse OC. Contraceptive, cerebral vein thrombosis and choked discs. Eur J Ophthalmol. 2007;17:669–70.

    CAS  Article  Google Scholar 

  30. 30.

    Ahmed H, Ali H. Risperidone induced weight gain leading to benign intracranial hypertension. BMJ Case Rep. 2011;2011.

  31. 31.

    Neely DE, Plager DA, Kumar N. Desmopressin (DDAVP)-induced pseudotumor cerebri. J Pediatr. 2003;143:808.

    Article  Google Scholar 

  32. 32.

    Friedman DI. Contemporary management of the pseudotumor cerebri syndrome. Expert Rev Neurother. 2019;19:881–93.

    CAS  Article  Google Scholar 

  33. 33.

    NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014;311:1641–51.

  34. 34.

    Smith SV, Friedman DI. The idiopathic intracranial hypertension treatment trial: a review of the outcomes. Headache. 2017;57:1303–10.

Download references


We would like to thank Dr Amin Bahubeshi, resident physician in Dermatology, for assisting with reviewing the manuscript. We would also like to thank Ms Marie-Cécile Domecq, University of Ottawa librarian, for helping with the search using MEDLINE, EMBASE, and Cochrane Review Database.

Author information




Dr. MGT—drafting and critical revision of manuscript for important intellectual content, and final submission of manuscript. Dr. BW—study concept and design, adjudication of abstracts, acquisition of data, analysis and interpretation, drafting of manuscript. Dr. WBK—acquisition, analysis and interpretation of data, drafting of manuscript. Dr. MtH—critical revision of the manuscript for important intellectual content. Dr. JB—study concept and design, adjudication of abstracts, critical revision of the manuscript for important intellectual content, study supervision.

Corresponding author

Correspondence to Jennifer Beecker.

Ethics declarations


No funding was provided in support of the research completed in this manuscript.

Conflict of interest

The authors, Marcus G. Tan, Brandon Worley, Whan B. Kim, Martin ten Hove, and Jennifer Beecker have no conflicts of interest to declare.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 191 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tan, M.G., Worley, B., Kim, W.B. et al. Drug-Induced Intracranial Hypertension: A Systematic Review and Critical Assessment of Drug-Induced Causes. Am J Clin Dermatol 21, 163–172 (2020).

Download citation