At the 2014 meeting of the International College of Neuropsychopharmacology, researcher Rieva et al. reported that 60% of bipolar patients with comorbid alcohol abuse have attempted suicide, and 48% of bipolar patients with cocaine abuse have attempted suicide. Thus, both of these comorbidities deserve specific attention and treatment. Unfortunately there are currently no Federal Drug Administration–approved drugs for bipolar patients with these comorbidities. The most promising treatments, based on data in patients with primary addictions, are the nutritional supplement N-acetylcysteine and topiramate, which have both performed better than placebo in studies of alcohol and cocaine abuse disorders.
Research on early-onset bipolar disorder sometimes lumps childhood-onset in with adolescent onset. Researcher Terence Ketter et al. explored differences in illness among 502 patients at the Stanford Bipolar Disorder Clinic. The 107 patients with childhood onsets (before age 13) had a more difficult course of illness in almost all domains compared to the 238 patients with adolescent onsets (age 13–18) or the 157 patients with illness onset in adulthood (after age 18).
Considered separately, both patients with childhood-onset illness and patients with adolescent-onset illness had more comorbid anxiety disorders, alcohol use disorders, eating disorders, prior suicide attempts, rapid cycling in the prior year, and at least five mood episodes over the course of their lifetimes than those patients whose illness began in adulthood. Patients whose illness began in childhood had higher rates of each of these unfavorable illness characteristics and were more likely to have a first-degree relative with a mood disorder.
These data mirror those from the Bipolar Collaborative Network in which this editor (Robert Post) is an investigator, and the larger STEP-BD network led by Perlis et al. All three suggest that in the US, two-thirds of the bipolar disorder seen in adults begins in childhood and adolescence, with about a quarter beginning before age 13.
Ketter suggests that research should not combine childhood and adolescent onset illnesses, which come with different rates of anxiety, alcohol, and eating disorder comorbidity, rapid cycling, and prior episodes. The statistical relevance of some findings can be diluted when the two groups are combined.
Editor’s Note: However, the primary message is that childhood onset bipolar disorder is a more severe version of the illness that deserves greater attention, treatment, and research so that its course can be made more benign. It is a problem that there are no Federal Drug Administration–approved treatments for children under 10 years of age with bipolar disorder.
Until now, there has been little research about treating obsessive compulsive symptoms in people with bipolar disorder.
In a recent four-month double-blind placebo-controlled randomized clinical trial presented by Sharaian et al. at the 2014 meeting of the International Society for Bipolar Disorders, topiramate was more effective than placebo at reducing these symptoms in patients with bipolar disorder when added to their regular treatment. Nine of 17 study participants responded to topiramate (53%), while only two of 16 responded to placebo (12.5%).
Editor’s Note: These findings add to the list of comorbidities that topiramate may help with, even though it does not have any efficacy in the treatment of mania itself. Topiramate has helped with avoidance of cocaine and alcohol, bulimia and weight gain, anger attacks, and now obsessive compulsive disorder (OCD). Topiramate is also FDA-approved for migraine prevention in adolescents and adults.
Many children with bipolar disorder also present with other comorbid Axis I psychiatric illnesses. Now it seems that the worsening of these comorbidities, such as attention-deficit hyperactivity disorder (ADHD) or an anxiety disorder, can signal a more difficult course of bipolar illness itself. At a symposium on the course of bipolar disorder in children at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), Shirley Yen from Brown University discussed findings on comorbidities of childhood onset bipolar disorder from COBY, the Collaborative Child Bipolar Network. Upon study entry, 60% of children with bipolar disorder also had ADHD, 40% had oppositional defiant disorder (ODD), 39% had an anxiety disorder, 12.5% had both oppositional defiant disorder and a conduct disorder, and 9% had a substance abuse disorder.
The prevalence of most of these comorbid illnesses increased over time (e.g. anxiety disorder rates increased from 39% to 62%). The illnesses were also related to the time it took participants to achieve recovery (eight consecutive weeks well), and the time until a recurrence of a depressive or manic episode.
Increases in anxiety were linked to longer time to achieve recovery and a shorter time to a recurrence. Increases in ADHD were linked to a more rapid onset of a depressive recurrence. Increases in oppositional defiant disorder and conduct disorder had no relationship with either remission or recurrence. Increases in substance abuse disorders were linked to a longer time to recover from a manic episode. Thus, worsening of the comorbid conditions had definite consequences for both recovery and recurrence.
A symposium on bipolar disorder and its comorbidities in children and adolescents was held at the annual meeting of the American Academy of Child and Adolescent Psychiatry in 2011. The following findings were reported there.
Researcher Janet Wozniak discussed the relationship of bipolar illness and attention deficit hyperactivity disorder (ADHD). Based on interviews of family members of children with bipolar illness alone, bipolar illness plus ADHD, ADHD alone, and controls, she concluded that bipolar illness occurred more often in families of children with bipolar illness with or without ADHD. Similarly, she showed that there was more ADHD in relatives of children with either ADHD alone or ADHD comorbid with bipolar illness. She concluded that the comorbidity of bipolar illness and ADHD is a unique subtype of bipolar disorder and requires further study.
Emotional Dysregulation and Substance Abuse
In another presentation, Tim Wilens indicated that those with bipolar disorder and emotional dysregulation had an 8- to 20-fold increased risk of having a substance abuse comorbidity with their bipolar disorder.
Substance Abuse Comorbidity
In a third presentation, Ben Goldstein reported that the onset of bipolar illness predates the onset of substance abuse in 60 to 83% of instances of comorbid illness. He emphasized the dramatic negative impact of comorbid substance use in children with bipolar disorder in terms of increasing legal entanglements, pregnancy, academic failure, suicide, and decreased compliance with medications. He reported that in the multi-site, National Institute of Mental Health (NIMH)-funded Course and Outcome of Bipolar Illness in Youth (COBY) study, the largest longitudinal study to date of youth with bipolar disorder, the risk of new onset substance abuse over the course of 4 years of follow-up was 32%. These data taken with the 15% of children who already had substance abuse at intake indicates that in this study approximately half of the children with bipolar illness had or acquired a substance abuse problem near the beginning of their illness. Two-thirds of the children in the study had abused both alcohol and cannabis. Read more
Maladaptive impulsive aggression often co-occurs with other psychiatric illnesses in children, so it can be difficult to find treatment solutions. A symposium at the 57th Annual Meeting of the American Academy of Child and Adolescent Psychiatry yielded some suggestions. Read on for an overview of impulsive aggression and possible treatment plans.
At the symposium, held in New York Oct. 26-31, 2010, panelists called maladaptive aggression the “fever” of child psychiatry (because it is common but also nonspecific) and described the phenomenon as “the language of the inarticulate.” The panelists drew a distinction between impulsive aggression, which describes behavior that is unplanned, unprofitable, and poorly controlled, and another phenomenon, predatory aggression, which describes behavior that is planned, sometimes profitable, and highly controlled.
The speakers on the panel indicated that impulsive aggression is related to other psychiatric syndromes including depression, attention deficit hyperactivity disorder (ADHD), mania, conduct disorder, oppositional defiant disorder, anxiety, post-traumatic stress disorder (PTSD), borderline personality disorder, autism, and schizophrenia. This raises problems for drug development, as Tom Laughren of the Federal Drug Administration (FDA) indicated in one talk at the symposium, because when new treatments are developed, they are studied in the context of only one primary disorder. Read more
Sherwood Brown and colleagues from the University of Texas Southwestern Medical Center have completed a successful placebo-controlled trial of citicoline for bipolar and unipolar depression with comorbid methamphetamine dependence. Forty-eight participants with methamphetamine dependence and either unipolar or bipolar depression were randomized to either citicoline (2000 mg/day) or placebo for 12 weeks. Those receiving citicoline had significantly greater improvement in scores on the Inventory of Depressive Symptoms compared with those who received placebo, and patients receiving citicoline stayed in the study significantly longer, with completion rates of 41% on citicoline and 15% on placebo.
In 2007, the same team of investigators reported in the Journal of Clinical Psychopharmacology that citicoline had positive effects in bipolar patients with cocaine dependence, who experienced significant decreases in cocaine use and fewer cocaine-positive urine tests while taking citicoline.
New research shows that there are more early onsets of illness and more difficult courses of bipolar illness in the US than in the Netherlands or Germany.
This editor was invited to give a plenary presentation at the 4th Biennial Conference of the International Society for Bipolar Disorders in Sao Paulo, Brazil in March. The talk, titled “A greater incidence of early onset bipolar illness and poor prognosis factors in patients in the US compared with those in The Netherlands and Germany,” was based on studies in our Bipolar Collaborative Network.
We found that patients who were studied and treated at four sites in the US (Los Angeles, Dallas, Cincinnati, and Bethesda) had more poor-prognosis factors and indices of difficult courses of bipolar illness compared with patients studied in the same fashion at three sites in Utrecht, the Netherlands and Freiberg and Munich, Germany. We presented some of these data in a preliminary report in the British Journal of Psychiatry in 2008 and further analyzed these data for an article published last year in the Journal of Clinical Psychiatry. Read more
Psychotherapy and psychoeducational approaches, long-term psychopharmacology, and combination therapy all play a role in preventing recurrent mood episodes.
Psychotherapeutic and Psychoeducational Approaches Are Critical
A number of studies presented at the 4th Biennial Conference of the International Society for Bipolar Disorders in Sao Paulo, Brazil in March indicated that cognitive-behavioral therapy (CBT) and individual and group psychoeducational approaches enhance both short- and long-term outcomes for patients with bipolar illness. These studies add to an already substantial literature that shows that focused psychotherapies (such as cognitive/behavioral, interpersonal, and social rhythms therapies) and psychoeducation are superior to treatment as usual.
These therapies can provide a variety of approaches to stress management and reduction, and can enhance family and interpersonal communication. Another way these focused psychotherapeutic approaches help patients is by demonstrating the benefits of effective long-term preventive treatment and encouraging its consistent use.
Without consistent prophylactic treatment, patients are at high risk for recurrences and their subsequent psychosocial and neurobiological consequences. Greater number of prior episodes is associated with an increased risk of psychosocial dysfunction, treatment resistance, cognitive dysfunction, medical comorbidities, and even dementia in old age.
After the jump: preventive psychopharmacology and combination therapy. Read more
Albert Arias and collaborators from the University of Connecticut Health Center presented a study of zonisamide in which the drug provided significant benefits over placebo in patients with primary alcoholism (i.e., not with comorbid bipolar illness). Treatments began at 100 mg/day and increased to a maximum of 500 mg/day.
EDITOR’S NOTE: If replicated, this study would place zonisamide in a category with topiramate (Topamax), which has also been shown to decrease alcohol intake and craving. Both drugs also share the ability to cause minor weight loss as a potentially positive side effect, and both drugs have also proven effective in double-blind studies in the treatment of bulimia.
However, four double-blind, placebo-controlled studies found that topiramate did not have acute antimanic efficacy. Zonisamide has not been studied in a systematic fashion, but open studies suggest its potential utility in mania and, to a lesser degree, in depression.
Since zonisamide may have positive effects on mood in patients with bipolar disorder, and there is now placebo-controlled documentation of its efficacy in primary alcohol abuse disorders, its ultimate potential utility in patients with bipolar disorder and comorbid alcoholism deserves consideration.