Ciclesonide as a manic trigger in a patient with long-term stable bipolar disorder: a case report

Adverse effects are frequent during systemic corticosteroid therapy, with the most common psychiatric effects being hypomania and mania.¹ Nasal corticosteroids may also have psychiatric effects. In addition to dose- and time-dependent risks, the incidence of psychiatric adverse effects may differ across different intranasal corticosteroid preparations and individual patients. However, whether a history of psychiatric disorder exacerbates the risk of adverse psychiatric reactions during corticosteroid therapy remains unclear.¹,²

To the best of our knowledge, this is the first report of an episode of mania triggered by the use of ciclesonide in a patient with bipolar disorder (BD). To date, the triggering of manic symptoms by steroid nasal sprays in patients with BD has been described in only two case reports.²,³

A 51-year-old married male dentist was diagnosed with BD 24 years prior to the event reported here. The natural history of the disease was characterized by depressive episodes, hypomanic episodes, and manic episodes with psychotic features, which were resistant to first- and second-line treatments, such as mood stabilizers and some second-generation antipsychotics. After several drug trials, optimal results were obtained using a combination of clozapine (100-150 mg/day) and fluvoxamine (100-250 mg/day), which he took for 17 years. During this period, he experienced only minor mood fluctuations, which were primarily attributed to life events.

In addition to his psychiatric disorders, he had chronic allergic rhinitis, which was primarily treated with montelukast and occasionally with antihistamines and low-dosage intranasal corticosteroids. He generally avoided corticosteroids, even at low doses, because they triggered transient subthreshold depressive symptoms and/or dysphoria.

For 2 years, he had been mostly well, with only transient subsyndromal depressive symptoms, until he experienced a severe bout of rhinitis accompanied by poor sleep, which was triggered by exposure to mold in a hostel. Six days after the rhinitis bout, he was prescribed ciclesonide (200 μg/day) for the first time. After 4 days of use, he experienced fluctuating manic symptoms, manifested by irritability, excitement, lability, amplified energy, inflated self-esteem, decreased need for sleep, pressure to keep talking, minor derailment, occasional fleeting delusions with themes of grandiosity, and paranoia. These symptoms were associated with impairment in social and occupational functioning. Approximately 10 days after the onset of the manic symptoms, he had a psychiatric consultation at our clinic and was advised to discontinue the use of ciclesonide, and an increased dose of clozapine was prescribed. Two days after ciclesonide discontinuation, all symptoms disappeared, and clozapine was decreased to the usual dose. During a 2.5-year follow-up period, the patient reported feeling well, with only minor and brief mood fluctuations, without repercussions in his conjugal, social, or professional life.

Intranasally administered corticosteroids exhibit a good safety profile, especially the new-generation drugs in this class, such as ciclesonide, fluticasone, and mometasone. Ciclesonide, a prodrug that is activated locally in the airway mucosa, is considered to be the safest intranasally administered corticosteroid.¹ Although the drug label reports symptoms of depression as one of the side effects of its nasal administration, other psychiatric symptoms remain unreported.⁴

We hypothesize that ciclesonide triggered the manic episode in our patient. Prior to ciclesonide administration, he had been stable for 2 years. He displayed good treatment adherence, did not use illicit drugs or alcohol, and had not experienced any significant life event. Since discontinuation of ciclesonide, the patient has remained asymptomatic for 2.5 years.

The two previous case reports of manic episodes triggered by intranasal steroids involved the use of beclometasone and mometasone by women aged 28 and 53 years, respectively.²,³ The first patient needed to be hospitalized for 2.5 weeks to receive antipsychotic and mood-stabilizer therapy. The condition of the second patient improved spontaneously within a few days of corticosteroid discontinuation. In the case reported herein, we decided to discontinue corticosteroid therapy and increase the dose of the antipsychotic agent because the course and treatment of intranasal corticosteroid-precipitated manic episodes in patients with BD are not well established. Sleep impairment, which can trigger mood-fluctuation episodes in patients with BD, is another aspect that is worth considering; in this case, it may be attributed to allergic sinusitis.⁵

This case report suggests that intranasal ciclesonide therapy can trigger manic episodes in patients with BD. Moreover, allergic sinusitis-related sleep problems may be a risk factor for manic episodes. Hence, psychiatrists should educate patients and their family members about the risks of intranasal corticosteroids.

References

• ¹
  Williams B, Smith WB, Kette FE. Intranasal ciclesonide for allergic rhinitis. J Asthma Allergy. 2008;1:49-54.
• ²
  Saraga M. A manic episode in a patient with stable bipolar disorder triggered by intranasal mometasone furoate. Ther Adv Psychopharmacol. 2014;4:48-9.
• ³
  Goldstein ET, Preskorn SH. Mania triggered by a steroid nasal spray in a patient with stable bipolar disorder. Am J Psychiatry. 1989;146:1076-7.
• ⁴
  Altana Pharma US. Ciclesonide nasal spray [Internet]. 2019 Oct 6 [cited 2020 Mar 26]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/022004lbl.pdf
  » http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/022004lbl.pdf
• ⁵
  Léger D, Annesi-Maesano I, Carat F, Rugina M, Chanal I, Pribil C, et al. Allergic rhinitis and its consequences on quality of sleep: an unexplored area. Arch Intern Med. 2006;166:1744-8.

Publication Dates

• Publication in this collection
  11 May 2020
• Date of issue
  Sep-Oct 2020

History

• Received
  11 Sept 2019
• Accepted
  14 Feb 2020