Neuropsychiatric Complications of Glucocorticoid Use

DOSE EQUIVALENCY:

Hydrocortisone (cortisol) 25mg= Prednisone 5mg= Methylprednisolone 4 mg= Dexamethasone 0.5 mg= Betamethasone 0.6 mg


AFFECTIVE, BEHAVIORAL, AND COGNITIVE CHANGES ASSOCIATED WITH STEROIDS

Rome and Braceland (1952) defined four grades of psychiatric responses in 20 patients receiving cortisone and ACTH:
* Grade 1: general feeling of well-being and stimulation, with improved concentration, energy, and clarity of thought.
* Grade 2: more distinct elevation of mood accompanied by restlessness, insomnia, increased motor activity, and accelerated mental activity.
* Grade 3: severe anxiety, ruminations, obsessions, mood swings, lethargy, indifference, crying spells, hopelessness and helplessness, excitement, restlessness, and flight of ideas.
* Grade 4: hallucinations, delusions, and “extreme variations in mood”.

Note: 60% fell into grades 1 and 2.
(Source: Am J Psychiatry 1952; 108:641– 651)

Lewis and Smith (1983) conducted a retrospective study of 14 cases and 79 published case reports of steroid induced psychiatric syndromes; and found:-
depression (35%), mania (31%), psychosis (14%), delirium (13%), and mixed states (6%).

(Source: J Affect Disord 1983; 5:319 –332)

The most common cognitive deficit: verbal or declarative memory.


DOSE–RESPONSE RELATIONSHIP

According to Boston Collaborative Drug Surveillance Program (studied 718 consecutive hospitalized patients receiving prednisone therapy in 1972):
Incidence of psychiatric symptoms in patients on:
40 mg/day: 1.3%
41–80 mg/day: 4.6%
>80 mg/day: 18.4%.

(Source: Clin Pharmacol Ther Sep–Oct 1972; 13(5):694 –698)

Also Lewis and Smith (1983) found that 77% of patients developed psychiatric symptoms when prednisone doses of >40mg is used.


TIME COURSE FOR DEVELOPMENT OF NEUROPSYCHIATRIC EFFECTS

According to Lewis and Smith (1983) patients developed symptoms:
- within first 6 weeks: 89%
- within the first 2 weeks: 62%
- within the first week: 39%

They found a median of 11.5 days (hours- 210 days) from initiation of steroid to development of neuropsychiatric manifestations.

>90% patients recovered from steroid related neuropsychiatric manifestations within 6 weeks.


CLINICAL PREDICTORS FOR NEUROPSYCHIATRIC EFFECTS

(A) STEROID DOSE:
- as discussed above

(B) GENDER:
- Female gender at risk.
- Lewis and Smith (1983) found that 68% of patients with psychiatric effects were women.
- This predominance persisted even when cases of SLE and rheumatoid arthritis were excluded.

(C) AGE:
- Age has been not reported as risk factor.
- Lewis and Smith (1983) found mean age to be 39.6 years (range 8–71 years).

(D) LIVER OR RENAL DYSFUNCTION:
Patient with liver or renal dysfunction (as well as the elderly) have higher free levels (unbound by albumin or transcortin) of prednisolone, so may be at higher risk for side effects.

(E) BLOOD BRAIN DAMAGE & LOW SERUM COMPLEMENT:

Nishimura and associates conducted a prospective cohort study of risk factors for corticosteroidinduced psychiatric disorders in patients with SLE. They identified blood brain barrier damage (odds ratio [OR] 33.3) and low serum complement levels (OR 0.91) as independent risk factors for steroid-induced neuropsychiatric disturbances.

(Source: Psychoneuroendocrinology 2008; 33(3):395–403)



1. Discontinue steroids, OR
2. Decrease dose <40 mg/day of prednisone equivalent.
3. No FDA Approved medication available.

ANTIDEPRESSANTS:
- Most studies warn against the use of TCAs: because of anticholinergic effects exacerbating delirium and worsening of symptoms could occur.
- Case reports of success with SSRI and SNRI, but no clinical trial done.

MOOD STABILIZERS:
- Reports of success with Lithium, Valproate and Lamotrigine.
- Clinical trial done by Falk et al compared 27 patients (given lithium before corticosteroids) with 44 controls (receiving only corticosteroids).
No patients in the lithium treated group developed psychiatric symptoms, and 6/44 (14%) of the controls developed psychosis.

Source: JAMA 1979; 241:1011–1012

ANTIPSYCHOTICS:
- Low dose antipsychotics are effective.
- Davis et al found that low-dose neuroleptic treatment led to resolution of psychotic symptoms in 83% of patients (24/29):-
*33% responded in 3 days
*60% improved in 1 week
* 80% have resolution of symptoms in 2 weeks.

Source: Psychiatr Ann 1992; 22:487–491

(For details please refer to: Psychosomatics 2012:53:103–115)