David Baxter PhD
Late Founder
Understanding the Switch Process in Bipolar Disorder
By Hannah Dunbar
Wednesday, June 9, 2010
Note: Hannah Dunbar is a summer research student from Oral Roberts University. Today she will be summarizing some of the key issues in the neurobiology of the switch process in bipolar disorder. Bipolar disorder is a somewhat unique mental disorder in that the onset of a mood swing can be quite dramatic--a patient with bipolar disorder can be fine one day and manic the next. It is important to try to understand the pathophysiology behind this rapid switch mechanism.
Introduction:
Dr. Giacomo Salvadore, M.D. from the NIMH along with colleagues from NIMH, Johnson & Johnson and Roche Pharmaceuticals recently published an excellent summary of the switch process in bipolar disorder. No uniform definition exists for ?switching? seen in bipolar patients, so Dr. Salvadore and colleagues defined switching, as ?the sudden transition from a mood episode to another episode of the opposite polarity with an intervening period of no more than 1 month?. Further understanding of the mechanism of the switching process, will likely prove vital in understanding the pathophysiology of bipolar disorder. Dr. Salavodore and colleagues outlined the clinical predictors of switching, individual neurotransmitter systems and possible biological mechanisms.
Sleep deprivation and switch:
Sleep deprivation has also been proposed as a final common pathway leading to onset of mania, and can be triggered by many environmental stimuli, psychological, interpersonal, or pharmacological factors . Sleep deprivation produces an acute antidepressant response in as many as 80% of subjects with bipolar depression, and 60% of patients with unipolar depression. Spontaneous switch rates have also been correlated with sleep deprivation, with switch rates ranging from 10% to 30% in patients with BD. This phenomenon makes it important for patients with bipolar disorder to get regular sleep hours. They should avoid medications that produce insomnia (i.e pseudoephedrine, other stimulants) and be cautious when traveling across time zones. Psychological stress (i.e. death of a loved one or loss of job) may produce temporary insomnia resulting in a manic or depressive switch. Medical illnesses that cause insomnia (i.e. influenza) should be monitored for risk of mania induction.
Role of circadian rhythms:
Mania switches were also found to be correlated with circadian rhythm consistent with finding sleep deprivation as detrimental to mood stability in bipolar disorder. Increased nocturnal motor activity and decreased REM sleep in particular have been noted prior to a manic switch. Salvadore and colleagues noted interactions between sleep reduction and a sleep-sensitive circadian phase interval could promote switches from depression. One confounding clinical issue is whether circadian rhythm disruptions proceed or follow the onset of mania. It is possible all the changes in sleep and biological clock function are secondary to the primary mood disturbance.
Antidepressants and switch:
Antidepressant drugs have been found to induce switching in 10% to 70% of patients. Clinicians and patients should know that treating bipolar depression with antidepressants alone is not good practice due to this high switch rate. Important switch rate found in certain clinical trials of antidepressants may provide understanding of the neurobiology of the switch process by analyzing switch rates for antidepressants that target different specific neurotransmitter systems. Tricyclic antidepressants (TCAs) have been most closely associated with a high risk of switching. Selective serotonin reuptake inhibitors (SSRIs) appear to have a lower risk for switching than TCAs. New antidepressants with both serotonergic and noradrenergic effects may be more likely to induce a switch than SSRIs. Data from several genetic studies investigating polymorphisms involved in the homeostasis of the serotonergic system, suggested it as having a negligible role in the switch process in bipolar disorder, with one exception. Mundo and colleagues found that short allele polymorphism of the serotonin transporter (5-HTTLPR) was overrepresented in the patients who developed a switch after receiving SSRIs. However these correlations were not confirmed in subsequent studies.
Dopaminergic agonists (psychostimulants) and switch:
Several dopaminergic selective drugs, such as psychostimulants have long been associated with high rates of switching and have been empirically tested in preclinical studies. Patients should be cautioned about the risk of switching with use of cocaine, methamphetamine and ecstasy. Additionally, dopaminergic drugs commonly used for Parkinson's disease may also induce mania.
Summary:
Patients and clinicians should be alert to potential triggers for mood disorders in bipolar disorder. Sleep and circadian rhythm problems appear to be a common trigger. Disruption of a variety of neurotransmitter systems may also contribute to the switch phenomenon. Further research will be needed to extend our knowledge of the switch process in bipolar disorder.
Source
Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, & Zarate CA Jr (2010). The neurobiology of the switch process in bipolar disorder: a review. The Journal of clinical psychiatry PMID: 20492846
By Hannah Dunbar
Wednesday, June 9, 2010
Note: Hannah Dunbar is a summer research student from Oral Roberts University. Today she will be summarizing some of the key issues in the neurobiology of the switch process in bipolar disorder. Bipolar disorder is a somewhat unique mental disorder in that the onset of a mood swing can be quite dramatic--a patient with bipolar disorder can be fine one day and manic the next. It is important to try to understand the pathophysiology behind this rapid switch mechanism.
Introduction:
Dr. Giacomo Salvadore, M.D. from the NIMH along with colleagues from NIMH, Johnson & Johnson and Roche Pharmaceuticals recently published an excellent summary of the switch process in bipolar disorder. No uniform definition exists for ?switching? seen in bipolar patients, so Dr. Salvadore and colleagues defined switching, as ?the sudden transition from a mood episode to another episode of the opposite polarity with an intervening period of no more than 1 month?. Further understanding of the mechanism of the switching process, will likely prove vital in understanding the pathophysiology of bipolar disorder. Dr. Salavodore and colleagues outlined the clinical predictors of switching, individual neurotransmitter systems and possible biological mechanisms.
Sleep deprivation and switch:
Sleep deprivation has also been proposed as a final common pathway leading to onset of mania, and can be triggered by many environmental stimuli, psychological, interpersonal, or pharmacological factors . Sleep deprivation produces an acute antidepressant response in as many as 80% of subjects with bipolar depression, and 60% of patients with unipolar depression. Spontaneous switch rates have also been correlated with sleep deprivation, with switch rates ranging from 10% to 30% in patients with BD. This phenomenon makes it important for patients with bipolar disorder to get regular sleep hours. They should avoid medications that produce insomnia (i.e pseudoephedrine, other stimulants) and be cautious when traveling across time zones. Psychological stress (i.e. death of a loved one or loss of job) may produce temporary insomnia resulting in a manic or depressive switch. Medical illnesses that cause insomnia (i.e. influenza) should be monitored for risk of mania induction.
Role of circadian rhythms:
Mania switches were also found to be correlated with circadian rhythm consistent with finding sleep deprivation as detrimental to mood stability in bipolar disorder. Increased nocturnal motor activity and decreased REM sleep in particular have been noted prior to a manic switch. Salvadore and colleagues noted interactions between sleep reduction and a sleep-sensitive circadian phase interval could promote switches from depression. One confounding clinical issue is whether circadian rhythm disruptions proceed or follow the onset of mania. It is possible all the changes in sleep and biological clock function are secondary to the primary mood disturbance.
Antidepressants and switch:
Antidepressant drugs have been found to induce switching in 10% to 70% of patients. Clinicians and patients should know that treating bipolar depression with antidepressants alone is not good practice due to this high switch rate. Important switch rate found in certain clinical trials of antidepressants may provide understanding of the neurobiology of the switch process by analyzing switch rates for antidepressants that target different specific neurotransmitter systems. Tricyclic antidepressants (TCAs) have been most closely associated with a high risk of switching. Selective serotonin reuptake inhibitors (SSRIs) appear to have a lower risk for switching than TCAs. New antidepressants with both serotonergic and noradrenergic effects may be more likely to induce a switch than SSRIs. Data from several genetic studies investigating polymorphisms involved in the homeostasis of the serotonergic system, suggested it as having a negligible role in the switch process in bipolar disorder, with one exception. Mundo and colleagues found that short allele polymorphism of the serotonin transporter (5-HTTLPR) was overrepresented in the patients who developed a switch after receiving SSRIs. However these correlations were not confirmed in subsequent studies.
Dopaminergic agonists (psychostimulants) and switch:
Several dopaminergic selective drugs, such as psychostimulants have long been associated with high rates of switching and have been empirically tested in preclinical studies. Patients should be cautioned about the risk of switching with use of cocaine, methamphetamine and ecstasy. Additionally, dopaminergic drugs commonly used for Parkinson's disease may also induce mania.
Summary:
Patients and clinicians should be alert to potential triggers for mood disorders in bipolar disorder. Sleep and circadian rhythm problems appear to be a common trigger. Disruption of a variety of neurotransmitter systems may also contribute to the switch phenomenon. Further research will be needed to extend our knowledge of the switch process in bipolar disorder.
Source
Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, & Zarate CA Jr (2010). The neurobiology of the switch process in bipolar disorder: a review. The Journal of clinical psychiatry PMID: 20492846
