Hydrocortisone associated hypomania in a child responding to shifting back to prednisolone.

Dear Sir,

Steroid induced neuro-psychiatric manifestations are well described in the literature.[12] A variety of steroids including prednisone, methylprednisone, dexamethasone, and hydrocortisone have been implicated in the causation of steroid induced neuropsychiatric symptoms.[1] The most common risk factor for neuro-psychiatric manifestations associated with steroids is the dose of the steroids.[1] Some of the previous reports suggest that the adverse psychological reactions of steroids may be more common with hydrocortisone, compared to that of prednisolone.[3] A review[4] reported that adverse psychiatric manifestations were noted when dexamethasone was being tapered off, in patients who had tolerated prednisolone earlier and also did not show psychiatric manifestation later when they were again exposed to prednisolone.[56] In the same review, by referring to an unpublished data, authors suggested that some of the patients who developed behavioural symptoms with dexamethasone are able to tolerate prednisolone without recurrence of behavioural symptoms.[4] In this report we describe a case of a young boy who developed psychiatric symptoms when medications were changed from prednisolone to hydrocortisone, which subsided on switching back to prednisolone.

Master Y, 9-year-old boy, was diagnosed with nephrotic syndrome at the age of 4 years. Over the years he had multiple relapses of nephrotic syndrome and was prescribed oral prednisolone 60 mg/day, since 8 months prior to current presentation. About 2 weeks prior to the index presentation, he had exacerbation of symptoms in the form of facial puffiness and generalized edema of the whole body. Investigations revealed normal levels of blood urea and creatinine (37 mg/dl and 1.2 mg/dl), but a high degree of proteinuria (4+) and hypoalbuminemia (2.1 g/dl). In view of the relapse, he was admitted to the Paediatrics unit of the hospital. At the time of admission, he was receiving tablet prednisolone 60 mg/day, which was continued at the same dose for the next 3 weeks along with supportive management, but his renal parameters did not improve. In view of the same oral prednisolone was stopped and injectable hydrocortisone was started at the dose of 240 mg/day. Within 24 h of change of steroids, a change in the behaviour was noticed. He started to speak excessively, was restless, and had increased self-esteem, over-socialization, overplanning, overfamiliarity and social disinhibition. His mood was mostly irritable with intermittent cheerfulness. His sleep reduced significantly and appetite was increased. These symptoms kept on worsening for 2 days, led to difficulty in managing him in the ward and required a psychiatric consultation. There was no associated history of loss of consciousness, disturbances in cognitive functions, worsening of the primary renal disease during this period and any evidence of use of any other prescription medications, or licit and illicit substances. On mental status examination he was cheerful, restless, had increased speech output with pressure of speech, and increased self-esteem and overplanning. His cognitive functions were preserved. In view of the temporal correlation with starting of injectable hydrocortisone and behavioural symptoms, and absence of family history of psychiatric illness a possibility of steroid induced hypomania (F06.3) was considered. In liaison with the paediatrician, injectable hydrocortisone was stopped and patient was restarted on oral prednisolone at the previous doses of 60 mg/day. No psychotropics were advised. Over the next 4 days, patient's behavioural symptoms resolved completely. The patient maintained well on oral prednisolone later on.

There is limited data with respect to relationship of steroids and psychiatric manifestations in children. However, existing literature suggests that use of steroids in children is associated with neuro-psychiatric manifestations like insomnia, aggressive behavior, irritability, labile affect, grandiosity, pressured speech, agitation, depression and hallucinations.[6] Our case expands this litearature and suggests that hypomania may be associated with use of steroids in children.

Some of the existing data suggests that the incidence of psychiatric/psychological adverse reactions is more frequent with dexamethasone compared to prednisolone.[3] The occurrence of hypomanic symptoms in this young child without familial predisposition to bipolar disorder and quick resolution of symptoms with withdrawal of hydrocortisone, in the absence of worsening of physical status, use of other medications and lack of worsening of cognitive functions during the period of hypomanic symptoms implicates the role of hydrocortisone in the causation of these symptoms in the index case. An interesting aspect in this case was that hypomanic symptoms lasted for the duration when hydrocortisone was being given and was not encountered with an equivalent daily dose of prednisone[1] administered before or after the use of hydrocortisone. Although some of the previous reports[56] suggests that psychiatric manifestations can occur during withdrawal of hydrocortisone in patients who have tolerated prednisolone, we could not get any published reports which suggested development of psychiatric symptoms while starting hydrocortisone in patients who tolerate prednisolone.

This case brings forth a situation where change in type of corticosteroid being administered led to emergence of hypomanic symptoms. This happened when shift was made from prednisone, which is a long acting preparation to hydrocortisone, a short acting formulation, with dose of both the corticosteroids being equivalent. The mechanism of steroid induced psychiatric manifestations is not clear, but it is suggested that the psychiatric manifestations may be related to the level of free fraction of steroids in the plasma.[7] As the plasma protein bindings for hydrocortisone is suggested to be more than prednisolone,[8] it can be hypothesized that in view of the hypoalbuminemia in the index case, there was higher level of free fraction of steroids which could have contributed to development of hypomanic symptoms. The case highlights the fact that children can differentially develop psychiatric manifestations with different types of steroids even when used in equivalent doses. The paediatricians and physicians using steroids for various medical conditions must be aware of the same and should take the pharmacokinetics of the steroids into consideration while switching from one corticosteroid to the other.