Corticosteroids Glucocorticoids
Prednisolone/ Prednisone
Deltacortril Depo–Medrone
Psychiatric adverse effects are not uncommon in patients taking corticosteroids. Usually dose related, if serious psychiatric symptoms occur it is not advisable to suddenly stop the medication as sudden stopping or change of dose can trigger, or worsen psychiatric symptoms. Slow reduction and loving care of the distressed patient is needed.
The dose should be gradually reduced. Medical support should be obtained. It may be necessary to hospitalise the patient for their own safety. The excessive use of psychotropic medication is not necessary as long as the person can be calmed, possibly with the aid of short term tranquillisers. These become addictive if used for more than about 3 weeks. Most people regain their mental stability as the dose is lowered. A lowering of manic mood may be seen within a few days.
For those needing cortico-steroids long term it is advisable to develop strategies to cope with extreme feelings of distress, anxiety, mania or anger that may occur as the dose is raised. Finding the optimum level of dose that you can tolerate is of course important and helpful. Once you know this you can warn the doctors to enable better management of the medication and your illness.
Possibly taking up Tai Chi, Yoga, and learning how to relax, meditate and breathe in a rhythmic relaxed way could help at times of medication induced distress.
Few studies are carried out and there is little in recent literature compared to the high incidence of psychiatric adverse reactions to corticosteroids.
Dr Thomas Stuttaford wrote about steroid psychosis in The Times 25th November 1996 following the suicide, while on corticosteroids for asthma, of the famous photographer, Donovan. “short courses of high dose oral steroids can induce a wide range of psychiatric problems. changes in mood, either unreasonable elation or depression to the extent of producing feelings of hopelessness and suicidal thoughts, are the most common undesirable effects."
APRIL has been contacted by a nurse following her father’s suicide after suddenly stopping a dose of 40 mg a day for only two weeks of prednisolone. He had received no advice about slow reduction in spite of also being on inhaled steroids.
We were told by a lady who suffered steroid withdrawal psychosis, that she received an apology from the hospital after discharging her with abrupt cessation of corticosteroids. The hospital promised to re- train staff in light of her experience
Please note that from personal family experience of the founder of APRIL and the information received from the public, we believe excessive use of psychotropic medicines, in cases of psychiatric adverse drug reactions (ADRs) is unnecessary. The Mayo information is only a guideline. There is little or no scientific evidence to back up the need for anything other than vigilance and careful monitoring with just enough medication to calm the situation day by day, while the cortico-steroids are gradually reduced if this is possible.
Information from the manufacturer and the Mayo Clinic follows.
Alliance Pharmaceuticals data from the Association of British Pharmaceutical Industries web site www.medicines.org.uk
The data sheet known as the Summary of Product Characteristics (SPC) contains the following information.
The SPC can be accessed at: http://emc.medicines.org.uk/document.aspx?documentId=19308#CLINICAL_PRECAUTIONS
Excerpt from the SPC
4.8 Undesirable effects
A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
The incidence of predictable undesirable effects, including hypothalamic-pituitary adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment (see 'Special warnings and special precautions for use').
4.4 Special warnings and precautions for use
Patients/ and or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/ systemic exposure (see also section 4.5 pharmacokinetic interactions that can increase the risk of side effects), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/ withdrawal of systemic steroids, although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.
Caution is necessary when oral corticosteroids, including Deltacortril Enteric, are prescribed in patients with the following conditions, and frequent patient monitoring is necessary.
Psychiatric Adverse Effects of Corticosteroids From the Mayo Medical School (T.P.W.) and Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minn (J.M.B.)
Thomas P. Warrington, MD and
Dr Warrington is now with the University of Oregon School of Health Sciences, Portland
Individual reprints of this article are not available. Address correspondence to J. Michael Bostwick, MD, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 (e-mail: bostwick.john@mayo.edu).
Abstract
Psychiatric adverse effects during systemic corticosteroid therapy are common. Two large meta-analyses found that severe reactions occurred in nearly 6% of patients, and mild to moderate reactions occurred in about 28%. Although disturbances of mood, cognition, sleep, and behavior as well as frank delirium or even psychosis are possible, the most common adverse effects of short-term corticosteroid therapy are euphoria and hypomania. Conversely, long-term therapy tends to induce depressive symptoms.
Dosage is directly related to the incidence of adverse effects but is not related to the timing, severity, or duration of these effects. Neither the presence nor the absence of previous reactions predicts adverse responses to subsequent courses of corticosteroids.
Corticosteroid-induced symptoms frequently present early in a treatment cycle and typically resolve with dosage reduction or discontinuation of corticosteroids. In severe cases or situations in which the dose cannot be reduced, antipsychotics or mood stabilizers may be required. This review offers an approach to identifying and managing corticosteroid-induced psychiatric syndromes based on the type of symptoms and anticipated duration of corticosteroid treatment.,
In this article, we define clinically significant symptoms as those that disrupt patients' daily lives or cause duress to them or those around them. We characterize mild to moderate reactions as those representing changes in mood or behavior that do not reach the level of a diagnosable psychiatric disorder.
The most frequently identified symptoms include agitation, anxiety, distractibility, fear, hypomania, indifference, insomnia, irritability, lethargy, labile mood, pressured speech, restlessness, and tearfulness. Following the lead of Smyllie and Connolly,8 who in 1968 defined a severe reaction as “serious enough to require psychiatric advice and treatment,” we define a severe reaction as a constellation of major symptoms consistent with a diagnosable affective syndrome, psychotic disorder, delirium, or another psychiatric condition.
The most commonly reported corticosteroid-induced psychiatric disturbances are affective, including mania, depression, or mixed states. Most often, patients receiving short-term corticosteroid therapy present with euphoria or hypomania, whereas long-term therapy tends to engender depressive symptoms.9 Although mood disorders occur in the vast majority of cases, either delirium or frank psychosis, typified by hallucinations, delusions, and disorganized thought, is the presenting syndrome in a sixth of patients.10-12 Severe episodes of depression, mania, or psychosis frequently include suicidal ideation.
Management
Management strategies for corticosteroid-induced psychiatric disturbances are based almost entirely on case reports, anecdotal evidence, and a few small case series. Understanding of this topic has grown only slightly during the past 50 years.
Psychiatric disturbances that result from corticosteroid therapy commonly resolve slowly after discontinuation of the drug or reduction of the dosage.43 Symptom duration is highly variable. Patients with delirium commonly recover in a few days, whereas those with psychosis generally take more than a week to return to baseline.44,45 Depression, mania, or mixed affective states may take up to 6 weeks to resolve after discontinuation of the offending agent.
Initial treatment of corticosteroid-induced psychiatric disturbances should begin with cessation of the corticosteroids or reduction of the dosage. If cessation is not an option, the dosage should initially be tapered to 40-mg prednisone equivalents per day, followed by tapering to a physiologic dosage of 7.5-mg prednisone equivalents per day as quickly as is safe to do so.46
For patients who cannot tolerate corticosteroid cessation or dose reduction or who suddenly develop psychosis, severe agitation, aggressive behavior, or other intolerable symptom complexes, palliative pharmacotherapy is indicated, even though no definitive treatment has been identified. Myriad case reports have shown varying degrees of clinical success with mood stabilizers including lithium,47-50 carbamazepine,51 and valproic acid,52,53 with selective serotonin reuptake inhibitors (SSRIs) including fluoxetine54 and sertraline,55,56 and with venlafaxine,57 typical antipsychotics,51,58,59 and atypical antipsychotics.38,60-6
CORTICOSTEROID WITHDRAWAL
Although reduction or cessation of corticosteroids is the mainstay of treatment for corticosteroid-induced psychiatric reactions, caution is advised when making substantial or rapid reductions in corticosteroid doses, particularly for patients receiving long-term and high-dose treatments. For these patients, a taper is advised to prevent both physiologic and psychiatric corticosteroid withdrawal phenomena.66 An inappropriate taper can result in 3 types of difficulties67: (1) suppression of the hypothalamic-pituitaryadrenal axis (HPA) with the potential for secondary adrenal insufficiency, (2) recurrence of the disease for which the therapy was initiated, and (3) a corticosteroid withdrawal syndrome characterized by symptoms of adrenal insufficiency but with normal HPA function. Appropriate tapering is critical and should be based on total dosage, therapy duration, and corticosteroid type.
Severe HPA suppression and corticosteroid withdrawal syndrome are both characterized by lethargy, malaise, depression, anorexia, nausea, myalgia, and arthralgias. When corticosteroids are stopped entirely, HPA suppression and corticosteroid withdrawal syndrome can be distinguished only by biochemical testing. In this instance, the corticotropin stimulation test is used to evaluate the integrity of the HPA.67
Corticosteroid withdrawal syndrome presents most commonly with depression, anxiety, and fatigue,66 but mania68
http://www.mayoclinicproceedings.com/content/81/10/1361.full
Excerpts from and article in the British Medical Journal
Mitchell and O’Keane BMJ 1998;316:244-245 (24 January)
Glucocorticoid steroids affect behaviour and mood
Adrenal steroids are commonly prescribed drugs, the central effects of which are rarely alluded to in routine clinical practice or systematically investigated in medical research.
Glucocorticoids are important in the pathogenesis of depression, but this potentially serious psychological side effect is often overlooked in clinical practice. Up to 20% of patients on high dose glucocorticoids report psychiatric disorders including depression, mania, psychosis or a mixed affective state.
A recent double blind placebo controlled trial of corticosteroid administration in healthy individuals showed that 75% of subjects developed disturbances in mood and cognition, which reversed when steroids were stopped.
We do not know the characteristics of those who are vulnerable to adverse effects, but those with higher cumulative dosages appear to be most at risk
American Journal of Psychiatry
Am J Psychiatry 1984; 141:369-372
Reversible steroid dementia in patients without steroid psychosis
NR Varney, B Alexander and JH MacIndoe
Six patients developed dementia-like cognitive changes that appeared to result from administration of steroid medications. Four of the patients never showed symptoms of steroid psychosis; the remaining two continued to show steroid dementia well after their steroid psychoses had resolved. The dementia was characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance. All six patients eventually recovered normal mental status following discontinuation or reduction of steroid medications. Larger prospective studies are needed to determine the prevalence and nature of the syndrome
http://www.ajp.psychiatryonline.org/cgi/content/abstract/141/3/369
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