Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

Romain Icick; Ingrid Melle; Bruno Etain; Margrethe Collier Høegh; Sébastien Gard; Sofie R Aminoff; Marion Leboyer; Ole A Andreassen; Raoul Belzeaux; Chantal Henry; Thomas D Bjella; Jean-Pierre Kahn; Nils Eiel Steen; Frank Bellivier; Trine Vik Lagerberg

doi:10.3389/fpsyt.2022.813256

Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study

Front Psychiatry. 2022 May 3:13:813256. doi: 10.3389/fpsyt.2022.813256. eCollection 2022.

Authors

Romain Icick^{1

2

3}, Ingrid Melle^{1

4}, Bruno Etain^{2

3

5

6}, Margrethe Collier Høegh¹, Sébastien Gard^{3

7}, Sofie R Aminoff^{4

8}, Marion Leboyer^{2

9

10}, Ole A Andreassen^{1

4}, Raoul Belzeaux¹¹, Chantal Henry^{5

12}, Thomas D Bjella¹, Jean-Pierre Kahn¹³, Nils Eiel Steen^{1

4}, Frank Bellivier^{2

3

5

6}, Trine Vik Lagerberg^{1

4}

Affiliations

¹ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
² FondaMental Foundation, Créteil, France.
³ INSERM U1144, Université Paris Cité, Paris, France.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Université Paris Cité, Paris, France.
⁶ Assistance Publique - Hôpitaux de Paris, GH Saint-Louis - Lariboisière - F. Widal, Département de Psychiatrie, Paris, France.
⁷ Hôpital Charles Perrens, Centre Expert Trouble Bipolaire, Pôle de Psychiatrie Générale et Universitaire (3/4/7), Bordeaux, France.
⁸ Early Intervention in Psychosis Advisory Unit for South East Norway, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁹ Paris Est Créteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie Translationnelle, Créteil, France.
¹⁰ Assistance Publique - Hôpitaux de Paris (AP-HP), HU Henri Mondor, Département Medico-Universitaire de Psychiatrie et d'Addictologie (DMU ADAPT), Fédération Hospitalo-Universitaire de Médecine de Precision (FHU IMPACT), Créteil, France.
¹¹ Assistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Sainte-Marguerite, Pôle de Psychiatrie, INT-UMR 7289, CNRS, Aix-Marseille University, Marseille, France.
¹² Department of Psychiatry, Service Hospitalo-Universitaire, GHU Paris Psychiatrie & Neurosciences, Paris, France.
¹³ Université de Lorraine, CHRU de Nancy et Pôle de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy, Laxou, France.

Abstract

Objective: The potential role of sub-optimal pharmacological treatment in the poorer outcomes observed in bipolar disorder (BD) with vs. without comorbid substance use disorders (SUDs) is not known. Thus, we investigated whether patients with BD and comorbid SUD had different medication regimens than those with BD alone, in samples from France and Norway, focusing on compliance to international guidelines.

Methods: Seven hundred and seventy patients from France and Norway with reliably ascertained BD I or II (68% BD-I) were included. Medication information was obtained from patients and hospital records, and preventive treatment was categorized according to compliance to guidelines. We used Bayesian and regression analyses to investigate associations between SUD comorbidity and medication. In the Norwegian subsample, we also investigated association with lack of medication.

Results: Comorbid SUDs were as follows: current tobacco smoking, 26%, alcohol use disorder (AUD), 16%; cannabis use disorder (CUD), 10%; other SUDs, 5%. Compliance to guidelines for preventive medication was lacking in 8%, partial in 44%, and complete in 48% of the sample. Compliance to guidelines was not different in BD with and without SUD comorbidity, as was supported by Bayesian analyses (highest Bayes Factor = 0.16). Cross national differences in treatment regimens led us to conduct country-specific adjusted regression analyses, showing that (1) CUD was associated with increased antipsychotics use in France (OR = 2.4, 95% CI = 1.4-3.9, p = 0.001), (2) current tobacco smoking was associated with increased anti-epileptics use in Norway (OR = 4.4, 95% CI = 1.9-11, p < 0.001), and (3) AUD was associated with decreased likelihood of being medicated in Norway (OR = 1.2, 95% CI = 1.04-1.3, p = 0.038).

Conclusion: SUD comorbidity in BD was overall not associated with different pharmacological treatment in our sample, and not related to the level of compliance to guidelines. We found country-specific associations between comorbid SUDs and specific medications that warrant further studies.

Keywords: bipolar disorder; comorbidity; substance use disorder; tobacco smoking; treatment guidelines.