Steven Dilsaver, MD

Jane, who is 21 years old, was referred by her mother because of long-standing severe interpersonal, academic, and occupational impairment. She was euthymic on the day she presented.

Jane had a history of unstable relationships and impulsive, self-destructive behavior. She failed to achieve educational objectives and to maintain stable employment. From early adolescence, she was defiant. When she was 15 years old, her parents became so frustrated with her that they sent her to a residential treatment facility for troubled girls.

In the years before presentation, she abused alcohol and experimented with a number of substances, but had not done so for more than a year before the evaluation. She had 3 first-degree relatives, none of whom were known to have a mood disorder.

Jane had been assessed by mental health professionals, including psychiatrists, over the years. Information about previously rendered diagnoses was not available. She had received psychotherapy but not a somatic treatment.

When interviewed, Jane was asked whether she had ever had episodes of depressed, irritable, or elevated mood, or some combination of these, lasting a week or longer. She did not recall this being the case. She was then asked whether she had ever had 2- to 3-day episodes characterized by some combination of these mood states. She said she had brief episodes of affective disturbance since early adolescence. These episodes occurred every 1 to 2 weeks, lasted about 2 days, and were marked predominantly by depressed and irritable mood. On these days, Jane had particularly low self-esteem, slept about 3 hours more than usual, ate excessively, and had a low level of energy and psychomotor slowing in the morning and restlessness late in the day and at night.

During some of these brief periods of depression, there were times throughout the day when Jane had brief bursts of strangely elevated mood, had hypertalkativeness but not frank pressured speech, was distractible, and had racing and crowded thoughts. She had never had a hypomanic episode or psychotic features. Jane's presentation most closely conformed to the criteria for “recurrent brief depression,” as specified in Appendix B of DSM-IV-TR. She was viewed by her physician as having “recurrent mixed depression.”

Although Jane was euthymic, a decision was made to use a pharmacological intervention aimed at interrupting the cyclical process. She was treated with lamotrigine rather than lithium because of its tolerability. She was instructed to take morning doses as follows: 25 mg for 14 days, then 50 mg for 14 days, followed by 100 mg for 7 days, and then 200 mg thereafter. Jane tolerated the medication well. She had 1- or 2-day periods of mixed depression weekly through the fifth week of treatment. However, from that point onward, she was free of symptoms.

After 9 months of treatment, Jane stopped taking lamotrigine. She became very depressed on the second day. Her mother called Jane's psychiatrist asking for guidance; he recommended that Jane restart her medication, since she had missed only 2 doses. Within a day, she felt well and did not cycle into an episode until 6 months later, when she decided to stop taking the medication. Two days later, Jane was in crisis and her mother called the psychiatrist. He recommended she resume taking lamotrigine. The symptoms remitted within 1 to 2 days. The cyclical process did not recur during the following 2 months, at which point she was lost to follow-up.

Recurrent brief depression is defined as a phenomenon marked by the presence of impairing depressive episodes of at least 2 days’ duration that meet all criteria for MDD (except for the duration criterion) and that occur at least once a month for 12 consecutive months and are not associated with the menstrual cycle.

Recurrent brief depression was included in Appendix B of DSM-IV and is now included in the main body of DSM-5. Mixed depression was not included in DSM-IV, but it is part of the chapter on MDD in DSM-5.

Mixed depression was first described by Kraepelin,

 but the concept was ignored until quite recently.

 The diagnosis of mixed depression, as described in the literature in recent years, focuses on the admixture of subthreshold symptoms of hypomania in the context of DSM-IV–defined MDD. By this standard, Jane did not have mixed depression because she never had an episode lasting at least 2 weeks. However, she did meet the criteria for recurrent brief depression and had significant mixed features during these episodes.

 have proposed validated changes in the criteria for hypomania that apply to this case. Their data suggest that hypomania is reasonably defined without reference to duration and includes symptoms of overactivity, euphoria, or irritability along with any 3 DSM-IV–specified symptoms of hypomania that lead to subjective or social impairment. By this standard, Jane would be viewed as having recurrent brief mixed hypomania.

Jane was euthymic when she presented, yet a psychotropic was prescribed for the purpose of aborting a cyclical process. Lithium would have been a reasonable option.

 One might have also used divalproex. However, owing to its tolerability, lamotrigine was selected. Jane did well but had symptom relapse within 2 days on both occasions she stopped the medication; with resumption of treatment, she had prolonged asymptomatic periods. This strongly suggests that lamotrigine was causal in interrupting the cyclical process.

This case illustrates the value of assessing patients with histories of stormy interpersonal relationships, impulsive behavior, and low social function for the presence of brief, episodic affective disturbance. It also illustrates the importance of screening patients with brief episodes of depression for mixed features. The use of an antidepressant in an effort to abort the cyclical process might have further destabilized mood and worsened the course of illness.

Dr Dilsaver is former Professor of Psychiatry and Behavioral Health at the University of Texas, Houston. He is currently at the Imperial County Behavioral Health Services in El Centro, Calif. He is an author of more than 150 publications in the fields of child, adolescent, and adult psychiatry. His focus of attention is the phenomenology of affective illness. He reports no conflicts of interest concerning the subject matter of this case. 

 Angst J, Merikangas K, Scheidegger P, Wicki W. Recurrent brief depression: a new subtype of affective disorder. 

 Angst J. The history of the concept of recurrent brief depression. 

Carta MG, Altamura AC, Hardoy MC, et al. Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample. 

Pezawas L, Wittchen HU, Pfister H, et al. Recurrent brief depressive disorder reinvestigated: a community sample of adolescents and young adults. 

 LÃ¶vdahl H, Andersson S, Hynnekleiv T, Malt UF. The phenomenology of recurrent brief depression with and without hypomanic features. 

Benazzi F. Bipolar disorder-focus on bipolar II disorder and mixed depression. 

Angst J, Gamma A, Benazzi F, et al. Toward re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. 

 Angst J, Gamma A. A new bipolar spectrum concept: a brief review. Bipolar Disord. 2002;4(suppl 1):11-14. 10. Conominas A, Bonet P, Nieto E. Recurrent brief depression treated with lithium. 

Articles

This case study of a 21-year-old woman-referred by a relative because of long-standing severe interpersonal, academic, and occupational impairment-illustrates the importance of screening patients with brief episodes of depression for mixed features.

Recurrent Brief Mixed Depression

Eight-year-old John was brought to the clinic by his aunt because of his highly aggressive destructive behavior and sleeping problems. His parents had been killed in a car accident when he was 5 years old, and just a year later, he had witnessed the violent death of his uncle. When he was 7, he began having auditory hallucinations related to painful recollections. He was assessed using a structured diagnostic interview, and a diagnosis of PTSD with hallucinations was made. John also met the criteria for major depressive episode.

His aunt reported periods of “weird, crazily” elevated mood. She described him as being episodically grandiose, having a reduced need for sleep, exhibiting flights of ideas, and having periods of incredibly high energy and pressured speech. He was euphoric on presentation. A further diagnosis of mixed episode was rendered.

Because of the danger posed by his behavior, John was aggressively treated with the triad of 2 mg of prazosin, 750 mg of extended-release divalproex (approximately 20 mg/kg), and 10 mg of aripiprazole given at 6 pm. A follow-up call was made on day 2 (following receipt of 1 dose of each medication). John’s aunt reported that he had slept 10 hours and awoke “in good spirits.”

When seen in clinic on day 8, John was no longer hallucinating and was sleeping about 10 hours a night. However, he continued to have periods of elevated mood and grandiosity, as well as periods of depressed, anxious, and irritable mood. He could not sit still. There were no changes made to his medications.

, blood work showed that John’s valproate level was 133 µg/mL, and there were no adverse effects. He had a 2- to 3-hour phase delay in the onset of sleep and woke intermittently throughout the night; his mood was still elevated at times. The dose of aripiprazole was raised to 15 mg.

When his aunt became ill and could not care for him, he was placed in a facility for homeless children. At this point, his treatment was interrupted, and John was lost to follow-up for 73 days. When brought to the clinic by staff at the facility on 

, John-who had not been treated for a prolonged period-was irritable, impulsive, and threw objects about. He was sleeping 2.5 to 3 hours nightly. He said he was thinking “real fast” and commented, “I am mad.” John was a ward of the court and treatment could not be resumed without judicial approval.

 with prazosin (2 mg), divalproex (750 mg), and aripiprazole (15 mg) given at 6 pm. Shortly after the resumption of treatment, John went to live with his grandmother. By 

, symptoms of mixed episode had resolved, and he no longer had nightmares or experienced auditory hallucinations. However, a structured screen for ADHD revealed that 16 of the 18 symptoms in the operational definition of ADHD were, “often” or “very often” present.

Lisdexamfetamine, 30 mg given at 7 am, was added to the treatment regimen. After taking this medication for about a week, John became aggressive: grasping a knife, he declared that he wanted to stab himself and another boy. The stimulant was discontinued.

, 4 days after stopping the lisdexamfetamine, his grandmother commented, “He has become the sweet little boy he is by nature.” Blood work showed a valproate level of 99 µg/mL.

John remained very inattentive and hyperactive despite not having symptoms of PTSD or an affective disorder. Because he was too disruptive to attend public school, John was homeschooled by his grandmother. Treatment with 5 mg of extended-release dexmethylphenidate was started on 

, John’s grandmother reported that his attention was improved and he was able to complete an assignment on his own.

, John’s grandmother reported that he had become easily frustrated, inattentive, and excessively active. The dose of dexmethylphenidate was increased to 10 mg. On 

, his grandmother reported a generally favorable effect of medication. However, because by early afternoon his inattentiveness often returned, the dose was raised to 15 mg.

, when last seen, John had been doing well for 3 weeks. His regimen consisted of 2 mg of prazosin, 750 mg of extended-release divalproex, and 15 mg of aripiprazole given at 6 pm, and 15 mg of dexmethylphenidate given at 7 am. The only adverse effect was a 3.5% weight gain over 104 days.

John presented a complex clinical picture. His behaviors might have led one to suppose he had ADHD-combined or primarily hyperactive type and conduct disorder. However, there was a strong history of trauma and an affective disturbance that included not only irritable but also depressed and euphoric mood along with grandiosity, and the results of the structured interview indicated that he formally met the criteria for both PTSD and mixed episode at presentation. If not for the use of a structured interview format, the features defining these disorders might have been missed and the child treated only for ADHD. His final diagnoses were PTSD, bipolar I disorder, mixed episode in remission, and ADHD-combined type.

Dr Dilsaver is former Professor of Psychiatry and Behavioral Health at the University of Texas, Houston. He is currently at the Imperial County Behavioral Health Services in El Centro, Calif. He is an author of more than 150 publications in the fields of child, adolescent, and adult psychiatry. His focus of attention is the phenomenology of affective illness. He reports no conflicts of interest concerning the subject matter of this Case Report. 

This child's behaviors suggested ADHD-combined or primarily hyperactive type and conduct disorder. However, there was a strong history of trauma and affective disturbance. A structured interview format indicated that he formally met criteria for both PTSD and mixed episode. Without this format, features defining these disorders might have been missed and the child treated only for ADHD.

Author | Steven Dilsaver, MD

Articles

Recurrent Brief Mixed Depression

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