Solifenacin as Add-on Therapy for Overactive Bladder Symptoms in Men Treated for Benign Prostatic Hyperplasia – Full Text View – ClinicalTrials.gov

Of note, >>[p]atients with orthostatic hypotension, ulcerative colitis, hyperthyroidism, dementia or cognitive dysfunction, Parkinson’s disease, or cerebrovascular disorder<< were excluded. How many real-life patients with BPH also have one of the above?

Solifenacin as Add-on Therapy for Overactive Bladder Symptoms in Men Treated for Benign Prostatic Hyperplasia – Full Text View – ClinicalTrials.gov.

Solifenacin as Add-on Therapy for Overactive Bladder Symptoms in Men Treated for Benign Prostatic Hyperplasia

This study has been completed.
Sponsor:
Information provided by:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00771394
First received: October 9, 2008
Last updated: March 3, 2010
Last verified: March 2010
  Purpose

To evaluate the efficacy and safety of solifenacin succinate as add-on therapy for overactive bladder (OAB) symptoms in men who have been treated for benign prostatic hyperplasia (BPH) with tamsulosin hydrochloride for at least 6 weeks

Condition Intervention Phase
Benign Prostatic Hyperplasia
Benign Prostatic Hypertrophy
Overactive Bladder
Drug: Tamsulosin hydrochloride
Drug: Solifenacin succinate
Phase 4
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study of Solifenacin Succinate as Add-on Therapy for Overactive Bladder (OAB) Symptoms in Men Treated for Benign Prostatic Hyperplasia (BPH) With Tamsulosin Hydrochloride
Resource links provided by NLM:
Further study details as provided by Astellas Pharma Inc:
Primary Outcome Measures:

  • Change from baseline in mean number of urgency episodes per 24 hours [ Time Frame: at 4, 8, 12 week ] [ Designated as safety issue: No ]
Secondary Outcome Measures:

  • Mean number of micturitions per 24 hrs [ Time Frame: at 4, 8, 12 week ] [ Designated as safety issue: No ]
  • Mean number of incontinence episodes per 24 hours [ Time Frame: at 4, 8, 12 week ] [ Designated as safety issue: No ]
  • Mean number of micturitions per night [ Time Frame: at 4, 8, 12 week ] [ Designated as safety issue: No ]
  • Adverse Events, Laboratory Tests [ Time Frame: end of study ] [ Designated as safety issue: No ]
Enrollment: 638
Study Start Date: October 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1. Tamsulosin alone Drug: Tamsulosin hydrochloride

oral
Other Names:

  • Harnal
  • YM617
Experimental: 2. Tamsulosin + solifenacin (low dose) Drug: Tamsulosin hydrochloride

oral
Other Names:

  • Harnal
  • YM617

Drug: Solifenacin succinate

oral
Other Names:

  • Vesicare
  • YM905
Active Comparator: 3. Tamsulosin + solifenacin (high dose) Drug: Tamsulosin hydrochloride

oral
Other Names:

  • Harnal
  • YM617

Drug: Solifenacin succinate

oral
Other Names:

  • Vesicare
  • YM905

Detailed Description:

Study drugs are administered for 14 weeks in total, including a 2-week run-in period (single blind) and a 12-week treatment period (double blind). After written informed consent, study drugs for the run-in period are orally administered once daily after breakfast for two weeks to subjects who fulfill the inclusion and exclusion criteria. Then, subjects are randomized and orally treated with study drugs for the treatment period once daily after breakfast for 12 weeks

  Eligibility

Ages Eligible for Study: 50 Years and older
Genders Eligible for Study: Male
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

  • Patients with benign prostatic hypertrophy who have been treated with tamsulosin for at least 6 weeks
  • Patients with urgency episodes and frequent micturitions
  • Written informed consent has been obtained
  • Uroflowmetry-Q max ≥ 5 mL/sec, and Post Void Residual Volume < 50 mL

Exclusion Criteria:

  • Patients with suspected symptoms of OAB whose onset is only transient (drug-induced, psychogenic, etc.)
  • Patients with obvious stress urinary incontinence
  • Patients with complications or who have a past history of a bladder tumor
  • Patients with urethral stricture or bladder neck stenosis
  • Patients with a history of surgery causing damage to the pelvic plexus
  • Patients with history of hypersensitivity to α receptor blockers, a/b receptor blockers, or anticholinergic drugs
  • Patients with orthostatic hypotension, ulcerative colitis, hyperthyroidism, dementia or cognitive dysfunction, Parkinson’s disease, or cerebrovascular disorder
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771394

Locations
Japan
Chubu, Japan
Chugoku, Japan
Hokkaido, Japan
Kansai, Japan
Kantou, Japan
Kyushu, Japan
Shikoku, Japan
Touhoku, Japan
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Central Contact Astellas Pharma Inc
  More Information

No publications provided

Responsible Party: Director, Astellas Pharma Inc.
ClinicalTrials.gov Identifier: NCT00771394     History of Changes
Other Study ID Numbers: 905-JC-001
Study First Received: October 9, 2008
Last Updated: March 3, 2010
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Astellas Pharma Inc:

Vesicare
Solifenacin succinate
Tamsulosin
Overactive Bladder
BPH

Additional relevant MeSH terms:

Prostatic Hyperplasia
Hyperplasia
Hypertrophy
Urinary Bladder, Overactive
Prostatic Diseases
Genital Diseases, Male
Pathologic Processes
Pathological Conditions, Anatomical
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Tamsulosin
Quinuclidin-3′-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on September 30, 2012

Posted in Aging, Forensic Neuropsychiatry, Health, Psychiatry/Neurology | Tagged , , |

Antimuscarinic drugs for overactive bladder… [J Am Geriatr Soc. 2005] – PubMed – NCBI

Notice authors’ disclosures when reading this material.

Antimuscarinic drugs for overactive bladder… [J Am Geriatr Soc. 2005] – PubMed – NCBI.

J Am Geriatr Soc. 2005 Dec;53(12):2195-201.

Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients.

Source

Neuropsychology Division, Department of Neurology, Georgetown University School of Medicine, Washington, DC, USA. wnimail@aol.com

Abstract

Antimuscarinic agents are the predominant pharmacological treatment for patients with overactive bladder (OAB). These drugs are thought to act primarily through antagonism at muscarinic M3 receptors located at neuromuscular junctions in the human bladder detrusor muscle. Several of these drugs have been shown to be efficacious in ameliorating the symptoms of OAB in older patients, but most currently available agents lack selectivity for the M3 receptor subtype, and interaction with other muscarinic receptor subtypes throughout the body may adversely affect a variety of physiological functions and result in unwanted side effects, including cognitive dysfunction. With the recent availability of antimuscarinic agents that show increased selectivity for M3 receptors relative to other muscarinic subtypes, an invitational expert panel meeting was convened to review not only the mechanisms by which antimuscarinic agents could affect cognitive function, but also the published literature on cognitive adverse events. A review of the literature shows that the cholinergic system in the central nervous system (CNS) exerts a major influence on cognitive processes, in particular memory via M1 cholinergic receptors. In addition, recent evidence suggests a role for M2 receptors in mediating cognitive function. Thus, cognitive dysfunction (including memory loss) during treatment with nonselective antimuscarinic agents for OAB is of growing concern, particularly in older patients and those with mild cognitive impairment or dementia. Increased blood-brain barrier permeability, which can occur with advanced age and certain comorbidities, may also facilitate CNS access of antimuscarinic agents (regardless of their physiochemical properties) and add to antimuscarinic burden. On the basis of available evidence, antimuscarinic agents with selectivity for M3 over M1 and M2 receptors, limited CNS penetration, or both may therefore offer a favorable balance of efficacy in treating OAB together with a reduced risk of adverse cognitive events in the older population.

PMID:
16398909
[PubMed – indexed for MEDLINE]

LinkOut – more resources

 

Posted in Aging, Forensic Neuropsychiatry, Health, Psychiatry/Neurology | Tagged , , |

the psychiatryneurology.net – legal October 1, 2012

Edition of October 1, 2012 is out:

the psychiatryneurology.net – legal.

Posted in Events, News, Psychiatry/Neurology | Tagged , , |

The Neuropsychiatric Sequelae of Steroid Treatment

Possible memory impairment from “nasal spray”?

Nice overview and bibliography.

Source URL: http://www.dianafoundation.com/articles/df_04_article_01_steroids_pg01.html

_____________________________________________________________________________________

The Neuropsychiatric Sequelae of Steroid Treatment

Benjamin H. Flores, MD and Heather Kenna Gumina, MA
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA

INTRODUCTION

The neuropsychiatric sequelae of steroid treatment are a common occurrence. Despite over 50 years of being described in the scientific literature, these sequelae are described predominantly via case reports with an overall paucity of more rigorous scientific studies being initiated and published on this topic.

“…the specific types of neuropsychiatric impairments comprise a range of symptoms from anxiety, irritability and impaired cognition to depression, mania, psychosis, and suicidality. ”

The following review of the topic of the neurpsychiatric sequelae of steroid treatment is based on a review of the PubMed database. Over 80 scientific articles on this topic were found and they encompass approximately the last 30 years of published research. In reviewing these articles, several conclusions can be made. First, the neuropsychiatric complications of steroid treatment are quite common. Second, the specific types of neuropsychiatric impairments comprise a range of symptoms from anxiety, irritability and impaired cognition to depression, mania, psychosis, and suicidality. Third, although the available literature fails to reveal a uniform approach to the treatment of these specific side effects, it is clear that these symptoms are common enough and potentially very severe so as to warrant aggressive and early intervention by psychiatric consultants. Lastly, given the overall lack of published scientific literature on this topic, it behooves patients, family, and care-providers to work to improve public knowledge with the goals of stimulating further research on this subject as well as improving the quality of care for patients with this condition.

THERAPEUTIC USES AND BENEFITS OF STEROID TREATMENT

The clinical uses of steroid treatment are varied and comprise a variety of different medical conditions. Steroid treatment is indicated in the management of immunologic disease such as systemic lupus erythematosus and Churg-Strauss Syndrome1, 2. They are also indicated in the management of respiratory conditions such as asthma and chronic obstructive pulmonary disease3. In addition, steroids are indicated in the treatment of a number of different types of cancer such as Non-Hodgkin’s Lymphoma4, 5. Furthermore, steroids are a common treatment intervention in a variety of musculoskeletal disorders such as acute and chronic back pain6, 7. Of note, most reviews of the use of steroids in the management of non-psychiatric illness do include at least a mention of the possible occurrence of steroid psychosis with this treatment modality.

COMMON OCCURRENCE AND RAPID ONSET

A review by Steiffel and colleagues4 reported a 5-10% occurrence of major psychiatric symptoms among cancer patients treated with high dose steroids. Lewis and Smith8reported an approximately 6% incidence of severe psychiatric syndromes among those undergoing treatment with steroids. The Boston Collaborative Drug Surveillance Program9reported an occurrence of psychiatric reactions in 1.3% of patients receiving 40mg/day or less, 4.6% of patients receiving 41 to 80mg/day, and 18.4% of those receiving 80mg/day or more of prednisone. A number of studies have suggested that the psychiatric side effects of steroid treatment have a rapid onset8, 10-13. Naber et al.12 reported that all patients treated with steroids who developed psychiatric symptoms had an onset within three days of initiation of treatment. Similarly, Wolkowitz et al.14reported an onset of psychiatric sequelae within five days of treatment with steroids among healthy subjects. Hall et al.11noted that 86% of patients with psychiatric manifestations of steroid treatment developed these symptoms within one week of start of treatment.

SPECIFIC SYMPTOMS

Cases of steroid-induced psychiatric symptoms have been reported in the literature since the 1950s. The variety of clinical signs associated with steroid-induced psychosis is comprised of visual and auditory hallucinations, delusional thinking, paranoia, affective disturbances (depression, apathy, hypomania, panic), depersonalization, motor disturbances (overactivity, immobility), aggressive behavior, and cognitive impairment11, 15-19. However, a number of publications on this topic appear to support symptoms of mania as being the most common psychiatric manifestation of steroid treatment8, 12, 20, 21. In contrast, some studies have suggested that the risk of depression increases with prolonged or chronic exposure to exogenous steroids22, 23. Nonetheless, early studies by Rome and Braceland16described four grades of psychological responses to steroids, which they felt were prototypical of all clinical presentations (Table 1).

Table 1: Clinical Classification of Psychological Response to Steroids
Grade Definition
1 Mild euphoria, lessened fatigue, improved sensation, increased sense of intellectual capacity.
2 Heightened euphoria. Patients are effusive, expansive, volatile, hypomanic, exhibit flight of ideas, impaired judgment, refractory insomnia.
3 Difference responses to reflecting the ego characteristics of the patient, such as anxiety, phobia, rumination, obsessional preoccupation, hypomania, or depression.
4 Grossly psychotic reaction with hallucinations, delusions, extreme variations in mood.
Data from Rome & Braceland16

Ling and colleagues19reviewed 55 case reports of psychiatric disturbance in association with steroid therapy and found a 58% incidence of psychotic symptoms. Nearly 72% of the cases with psychotic symptoms also included mood symptoms. Lewis and Smith’s review8 of 79 case reports of psychiatric symptoms occurring in association with the use of steroids found a 71% incidence of psychotic symptoms. Mood symptoms were reported in over 75% of the 79 cases, and concurrent psychotic symptoms were present in over 66% of these cases. Gift and colleagues24found significantly greater self-reported depression scores among patients with chronic obstructive pulmonary disease (COPD) receiving prednisone compared to COPD patients not receiving any steroids. Interestingly, the psychiatric sequelae of steroid treatment are often sudden in onset and appear to generally occur within 2 weeks after steroid introduction19.

In our review of the literature since the work by Lewis and Smith8, 56 case reports have been published suggesting an association between psychiatric symptomatology and steroid treatment. In eight of these cases25-30, the development of psychiatric symptoms was more clearly associated with the withdrawal, than with the administration, of steroids. Interestingly, seven of these eight cases occurred in female patients. All eight cases included mood disturbance; 2 with depression, 4 with mania, and 2 with mixed state. Psychotic symptoms were reported in all eight cases, including hallucinations and delusions in 5 cases.
Forty-eight cases1-3, 31-50were identified where the development of psychiatric symptoms was clearly associated with the administration of steroids. Nearly 65% of these cases occurred in female patients, which appears to support the trend reported in the literature of the apparent greater incidence of this condition among women as opposed to men20. Ages ranged from 2.75 years to 71 years of age, with a mean of 40.9. Onset of symptoms in the 48 cases occurred between 1 and 60 days after initiation of steroid treatment, with a mean of 15.4 days

Psychotic symptoms were reported in 64.6% of these 48 cases, similar to the incidence of psychotic symptoms reported by Ling and colleagues19 (58%), as well as Lewis and Smith8 (71%). In those cases reporting specific psychotic symptoms (19 cases), hallucinations occurred in 57.9% of the cases and delusions occurred in 73.7% of the cases. Among the cases reporting presence or absence of mood symptoms (45 cases), mania was observed in 47.7%, depression in 25.0%, and mixed state in 9.1%. The remaining 18.2% of cases reported psychosis or delirium in the absence of mood symptoms.

Studies by Wolkowitz and colleagues13, 14reported reversible cognitive deficits and mood symptoms in healthy control subjects after administration of prednisone and dexamethasone. Newcomer and colleagues also found significant reversible cognitive deficits in healthy controls given dexamethasone and hydrocortisone51, 52.

Steroid-induced cognitive deficits appear to be fairly specific for declarative or verbal memory14, 51-55. However, the range of specific cognitive deficits appears to also include impairment in memory retention, attention, concentration, and occupational performance56. In addition, delirium (a syndrome characterized by disorientation and confusion) has also been reported as a consequence of steroid treatment39, 44. These cognitive deficits appear to reverse with the reduction or withdrawal of steroids; yet, there is also some suggestion that the risk of corticosteroid-induced cognitive impairment is greatest with increases or rapid changes in steroid dose13, 39, 44. Similar reversible and dose-dependent declarative memory deficits have been reported in persons with Cushing’s diseases57-59, suggesting that excess endogenous and exogenous steroids produce similar cognitive effects.

HIGH VERSUS LOW STEROID DOSES

There appears to be a dose-response relationship for psychiatric symptoms during steroid treatment. The Boston Collaborative Drug Surveillance Program9 reported an overall mean prednisone dose of 59.5mg/day in patients with psychiatric reactions. This study also found a striking dose-response relationship for acute psychiatric reactions as psychiatric reactions were found to occur in 1.3% of patients receiving 40mg/day or less, 4.6% of patients receiving 41 to 80mg/day, and 18.4% of those receiving 80mg/day or more. Similarly, Chan and colleagues60reported psychosis in 8% of patients receiving 90mg/day prednisone compared to 3% in patients receiving 30mg/day. Naber and colleagues12 used a semistructured interview and the Profile of Mood States to study the psychological and cognitive effects of high and low doses of steroids (methylprednisone or fluocortolone) in ophthalmologic patients, all of whom were free of psychiatric illness, and found that 36% developed mania or depression during high dose steroid treatment. Olsen and colleagues61found a significant dose-response relationship in relation to mood changes. Wada et al.20 also reported a strong association between high dose steroid treatment and rapid development of mood symptoms. In contrast, studies examining the consequences of low dose steroid treatment have found little or no psychiatric symptomatology18,62, 63.

In our review of 56 case reports published since the work by Lewis and Smith8, 48 of these were able to demonstrate a clear association between the onset of psychiatric symptoms and the administration of steroid treatment. Prednisone was the steroid in question in 37 of these case reports (47 reported the type of steroid), followed by methylprednisone (4), dexamethasone (4), betamethasone (1), and hydrocortisone (1). In the 41 case reports in which steroid dosage was included, we calculated prednisone-equivalent dosage for the non-prednisone cases, and found a range of 5 to 200mg prednisone per day, with a mean dose of 58.3mg per day. This mean prednisone-equivalent dosage appears to further support the suggestion by the literature that the association between psychiatric symptomatology and steroid administration is only apparent at higher dosages

PATHOPHYSIOLOGY

Overall, the pathophysiology of the neuropsychiatric sequelae of steroid treatment remains unclear. There may be a link between neuronal activation of dopaminergic and cholinergic systems and high corticosteroid levels in the brain64. In the psychiatric literature, excessive activation of the dopamine system is believed to underlie the pathophysiology of symptoms of mania, psychosis, and severe forms of depression such as psychotic depression. As such, it is hypothesized that excessive levels of corticosteroids cause an increase in dopamine levels, which in turn may result in symptoms of mania, psychosis and severe depression. In contrast, central and peripheral decreases in serotonin secretion have also been linked to steroid administration65. Similarly, the current psychiatric research literature suggests that diminished serotonin levels may play a role in a variety of psychiatric syndromes including clinical depression. Consequently, it is postulated that corticosteroid administration may result in symptoms of clinical depression via a reduction in serotonin levels.

Interestingly, Brown et al.11reported that patients receiving steroid treatment appear to demonstrate dose-dependent cerebral atrophy. In addition, they also review animal data, which show dose-dependent detrimental effects on learning and memory with exposure to high doses of steroids.

TREATMENT

Unfortunately, the available literature on the treatment of steroid-induced psychosis is limited and no uniform approach to the management of these symptoms is readily apparent.

Falk and colleagues66prophylactically treated patients receiving corticotrophin (a treatment which has a biological effect similar to steroid treatment) for multiple sclerosis or retrobulbar neuritis with lithium carbonate and compared them with similar patients not receiving concurrent lithium during steroid treatment, and found a 14% rate of onset psychosis in the group not receiving lithium compared to 0% of those receiving concurrent lithium. Likewise, a number of case reports have demonstrated successful treatment with lithium following the onset of depressive symptoms37, 46, 47.

Lewis and Smith8 report in their review of the literature that steroid taper alone appears to be effective in over 90% cases where this employed. In addition, they find a 100% effectiveness in cases where neuroleptics and steroid taper, or treatment with lithium alone, or treatment with ECT alone is initiated. In contrast, they also report an absence of clinical benefit for the treatment of steroid-induced psychosis with tricyclic antidepressants(amitriptyline, nortriptyline, desipramine, and imipramine are examples of tricyclic antidepressants). Hall et al.11, in fact, report a worsening of neuropsychiatric symptoms when patients were given tricyclic antidepressants and advocate for the primary use of antipsychotic agents in the management of this condition. However, several recent case reports have been published describing the successful treatment of steroid-induced depression with newer antidepressants, such as sertraline, fluvoxamine, and fluoxetine50, 65, 67. Furthermore, a recent report suggests the use of a combination of an antidepressant and antipsychotic in the treatment of steroid-induced psychotic depression2 (Lyster, 2002).

A review by Brown and Chandler2 suggests that the mainstays of the treatment of steroid psyhcosis should include taper or discontinuation of the steroid, treatment with lithium, or treatment with antipsychotics. They also recommend that other interventions such as antidepressants be used with caution and that the tricyclic antidepressants be avoided altogether because of concerns regarding their apparent lack of benefit and potential to worsen the symptomatology of steroid psychosis.

Review of the published literature suggests that antipsychotics, from haloperidol and promethazine to risperidone and olanzapine, are effective and can be safely administered in conditions such as euphoric mania, mixed-state mania (a condition characterized by both symptoms of depression and mania), prominent psychosis (delusional thinking or auditory and/or visual hallucinations), and delirium3, 17, 28, 30, 36, 39.

Overall, several patterns in the treatment of steroid psychosis do emerge. Specifically, it does appear clear that if neuropsychiatric sequelae of steroid treatment become apparent, then the steroid dose should be reduced and/or discontinued. However, if this is not possible, then pharmacotherapy is indicated. Toward this end, lithium appears to be indicated and safest in the management of symptoms of depression, whereas antipsychotics appear indicated in the treatment of mania and psychotic symptoms. It is noteworthy that the available literature suggests that lithium can be used effectively both in the treatment of acute symptoms, as well as in the prophylactic treatment of steroid psychosis. Recent case reports appear to suggest the safe and successful administration of SSRI antidepressants in the management of steroid-induced depression, as well as suggest the use of a combination of an antidepressant and antipsychotic as the optimum treatment of psychotic depression associated with steroid administration. Lastly, there are case reports regarding the effectiveness of benzodiazepines, such as alprazolam, clonazepam, and lorazepam, in the management of such specific steroid-induced symptoms as insomnia and anxiety45. Basically, this management approach is consistent with current pharmacotherapy approaches in psychiatry. In contrast, although there are data demonstrating the effectiveness of antidepressants in the management of steroid-induced depression, this class of medications should be used with caution as there is concern, particularly with the tricyclic class, that they may exacerbate this condition.

IMPORTANCE OF PSYCHIATRIC INTERVENTION

Brown and Chandler21 posit the importance of improving the scientific understanding of the neuropsychiatric consequences of steroid treatment as a means of improving patient care via improved disclosure of all of the potential side-effects of this treatment, as well as being a means of ensuring close monitoring of and early intervention in these potential side-effects.

The work by Lewis and Smith8 underscores the importance of early psychiatric intervention to minimize the morbidity and mortality associated with steroid treatment. Lewis and Smith8 report that among 79 cases of steroid-induced psychosis, 93% had a complete recovery, but 4% had continued symptoms or recurrence of symptoms and 3% committed suicide. With respect to the issue of suicidality, however, Stiefel et al.4 note an almost complete absence of data on the occurrence of suicide in the setting of steroid treatment. Wada et al.20 do find an association between an increased risk of suicidality and steroid treatment. In addition, Stiefel et al.4 do note a report by Memorial Sloan Kettering68 which shows an increased risk of suicide attempt among those treated with steroids who experience mild cognitive impairment and depression.

Overall and given the potential severity of neuropsychiatric symptoms associated with steroid treatment, it is strongly recommended that patients be monitored closely and that a low threshold for psychiatric consultation and intervention be observed.

DIRECTIONS FOR FUTURE RESEARCH

Brown and Suppes10 highlight various limitations of the current literature on the topic of the neuropsychiatric manifestations of steroid treatment. They emphasize that most large studies on this topic have not included formal psychiatric assessment or involvement in characterizing the nature of the various neuropsychiatric side effects. On the other hand, studies that do incorporate formal psychiatric assessment of neuropsychiatric side effects are small in size and, thus, the interpretation and generalizability of the results are difficult. In addition, Brown and Suppes10 suggest that studies on this topic need to systematically investigate potential risk factors such as the degree to which a personal or family history of psychiatric illness may contribute to the development of these sequelae. Interestingly, recent advances in the field of genetics may help reveal the role certain genes or their polymorphisms may play in the development of this condition both in individuals with and without a personal or family history of psychiatric illness.

Wada et al.20 suggest that furthers areas of investigation on this topic include study of the individual susceptibility for mania versus depression versus any other manifestation of this condition. Also, they recommend that further research be done to investigate the apparent greater occurrence of steroid-induced psychosis among women as compared to men. In addition, Wada et al.20 note a paucity of information on the long-term outcome and risk of recurrence of these symptoms. There also exists very limited research on the optimum treatment interventions of the various and specific manifestations of steroid-induced psychosis 20.

Furthermore, it should also be emphasized that there is an overall dearth of research on the topic of the neuropsychiatric side effects of steroid treatment. For example, whereas over eighty articles were found on this topic in the PubMed database for the last almost 30 years, the number would certainly be in the thousands if one were searching for articles on the topic of say the many benefits to steroid treatment in oncology. In other words, a medical topic with an adequate amount of interest and effort applied to furthering the understanding thereof should generate much more in the way of scientific study. Therefore, it is also the goal of the current review to demonstrate the tremendous need for further interest in and study of the common occurrence of the neuropsychiatric consequences of steroid treatment.

CONCLUSION

The neuropsyhciatric sequelae of steroid treatment are a common occurrence. Despite over 50 years of being described in the scientific literature, these sequelae are described predominantly via case reports with an overall paucity of more rigorous scientific studies being initiated and published on this topic.

In reviewing these articles, several conclusions can be made. First, the neuropsychiatric complications of steroid treatment are quite common. Second, the specific types of neuropsychiatric impairments comprise a range of symptoms from anxiety, irritability and impaired cognition to depression, mania, psychosis, and suicidality. Third, although the available literature fails to reveal a uniform approach to the treatment of these specific side-effects, it is clear that these symptoms are common enough and potentially very severe so as to warrant aggressive and early intervention by psychiatric consultants.

Lastly, given the overall lack of published scientific literature on this topic, it behooves patients, family, and care-providers to work to improve the promulgation of this knowledge with the goals of stimulating further research on this subject as well as improving the quality of care for patients with this condition.

Footnotes:

  1. Lopez-Medrano F, Cervera R, Trejo O, Font J, Ingelmo M. Steroid induced psychosis in systemic lupus erythematosus: a possible role of serum albumin level. Ann Rheum Dis. 2002;61(6):562-563.
  2. Ismail M, Lyster G. Treatment of psychotic depression associated with steroid therapy in Churg-Strauss syndrome. Ir Med J. 2002;95(1):18-19.
  3. Ahmad M, Rasul F. Steroid-induced psychosis treated with haloperidol in a patient with active chronic obstructive pulmonary disease. Am J Emerg Med. 1999;17(7):735.
  4. Stiefel F, Breitbart W, Holland J. Corticosteroids in cancer: neuropsychiatric complications. Cancer Invest. 1989;7(5):479-491.
  5. Brown E, Suppes T, Khan D, Carmody T. Mood changes during prednisone bursts in outpatients with asthma. Journal of Clinical Psychopharmacology. 2002;22:55-61.
  6. Curatolo M, Bogduk N. Pharmacologic pain treatment of musculoskeletal disorders: current perspectives and future prospects. The Clinical Journal of Pain. 2001;17:25-32.
  7. Deyo R. Drug therapy for back pain: which drugs helps which patients? Spine. 1006;21(24):2840-2849.
  8. Lewis D, Smith R. Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature. J Affect Disord. 1983;5(4):319-332.
  9. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther. 1972;13(5):694-698.
  10. Brown E, Suppes T. Mood symptoms during corticosteroid therapy: a review. Harv Rev Psychiatry. 1998;5(5):239-246.
  11. Hall R, Popkin M, Stickney S, Gardner E. Presentation of the steroid psychoses. J Nerv Ment Dis. 1979;167(4):229-236.
  12. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days’ corticosteroid treatment. A prospective study. Psychoneuroendocrinology. 1996;21(1):25-31.
  13. Wolkowitz O, Reus V, Weingartner H, et al. Cognitive effects of corticosteroids. Am J Psychiatry. 1990;147(10):1297-1303.
  14. Wolkowitz O, Rubinow D, Doran A, et al. Prednisone effects on neurochemistry and behavior: preliminary findings. Arch Gen Psychiatry. 1990;47(10):963-968.
  15. Lewis A, Fleminger J. The psychiatric risk from corticotrophin and cortisone. Lancet. 1954;20(226(6808)):383-386.
  16. Rome H, Braceland F. The psychological response to ACTH, cortisone, hydrocortisone, and related steroid substances. American Journal of Psychiatry. 1952;108(9):641-651.
  17. Brown E, Khan D, Nejtek V. The psychiatric side effects of corticosteroids. Ann Allergy Asthma Immunol. 1999;83(6):495-503.
  18. Bender B, Lerner J, E. K. Mood and memory changes in asthmatic children receiving corticosteroids. J Am Acad Child Adolesc Psychiatry. 1988;27(6):720-725.
  19. Ling M, Perry P, Tsuang M. Side effects of corticosteroid therapy: psychiatric aspects. Arch Gen Psychiatry. 1981;38(4):471-477.
  20. Wada K, Yamada N, Sato T, et al. Corticosteroid-induced psychotic and mood disorders: diagnosis defined by DSM-IV and clinical pictures. Psychosomatics. 2001;42(6):461-466.
  21. Brown E, Chandler P. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry. 2001;3(1):17-21.
  22. Herbert J. Neurosteroids, brain damage, and mental illness. Exp Gerontol. 1998;33(7-8):713-727.
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Ist WORLD SYMPOSIUM ON TRANSLATIONAL MODELS OF PANIC DISORDER- I Simpósio Internacional sobre Modelos Translacionais do Transtorno do Pânico

I Simpósio Internacional sobre Modelos Translacionais do Transtorno do Pânico.

 

I Simpósio Internacional sobre Modelos Translacionais do Transtorno do Pânico

Presentation

This year is the 20th anniversary of the two most influential theories on the etiology and brain mechanisms of panic disorder, namely, the THEORY OF THE DUAL ROLE OF SEROTONIN ON PANIC AND ANXIETY, proposed by John F. ‘Bill’ Deakin (UK) and Frederico G. Graeff (Brazil), and the FALSE SUFFOCATION ALARM THEORY, proposed by Donald F. Klein (USA), the discoverer of the therapy of panic disorder.

Therefore, the timing is perfect both to celebrate the 20th anniversary of these theories and discuss their impact and the latest fidings on panic disorder and comorbid diseases.

Accordingly, we are invinting you to participate in the “Ist WORLD SYMPOSIUM ON TRANSLATIONAL MODELS OF PANIC DISORDER” to be held at Vitória, Espirito Santo, Brazil, from 16th to 18th November, 2012.

Besides honoring the distinguished proponents of these theories, the symposium will promote the dialogue between the main current clinical and pre-clinical research groups on this issue. As well, this symposium highlights the 40 year’s outstanding contribution of Brazilian researchers to the understanding of the neural mechanisms underlying the development and therapy of anxiety disorders.

 

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