Chris Aiken, MD

Slideshows

A recent finding that ADHD can begin in adulthood has surprised researchers. Here are reasons why it may be wrong.

Discovery of Adult-Onset ADHD Raises Questions

7 Questions that Separate ADHD from Bipolar Disorder

What are they key differences between ADHD and bipolar disorder? How can they be identified? 

A single sentence in the landmark textbook 

by Frederick Goodwin, MD, and Kay Jamison, PhD, overshadows much of the progress we have made in treating bipolar disorder: “Complete symptomatic remission does not ensure functional recovery.”

 In other words, we can treat the symptoms but that does not mean our patients will get their lives back. Strained marriages, checkered work histories, and lost friendships become the norm.

For these patients, it is not the depression or the mania but the cognitive symptoms of bipolar disorder that get in the way. Memory, attention, and higher-order constructs like judgment and social intuition are among the impairments that can persist after symptomatic remission, and they do so in about 30% to 60% of cases. Compared to mood symptoms, cognitive problems are more difficult to treat, but they can be helped.

The first step is recognition. Clinicians should ask questions such as: “Now that the depression and mania have gone away, do you feel like your mind is working fully, or are there still areas of life where you are not functioning all the way?” From there, assess occupational functioning (eg, finishing tasks, prioritizing, and time management) and household chores (eg, bills, shopping, cleaning, and basic hygiene). Also inquire about hobbies and recreation as well as family, relationship/sexual, and social life (eg, have they lost interest, has enjoyment faded, can they follow a plot of a movie, are there problems in relationships?).

Although subjective assessments are important and provide information about quality of life, objective testing can also help better understand cognitive issues. The trail-making test and the digit symbol substitution test are easy to administer and give meaningful results. They are now available through a free software package, THINC-it (available online at progress.im), that can be used to track progress.

 is crucial; explain that it is common for these problems to continue even after the major episodes have resolved. Similarly, let them know that cognitive recovery is a slow process that requires their active involvement.It also helps for families to hear this message. Families need to allow opportunities for the patient to regain their skills in a judgment-free zone and accept the mistakes that come with these attempts. Too often those opportunities are blocked by criticism, blame, or family members who take over patients’ lives in a well-intentioned effort to prevent failure.

Patients often attribute cognitive problems to mood stabilizers. Although there is a grain of truth to this notion, the greater burden is from the episodes themselves. The strongest 

 of cognitive impairment is the number of past episodes, and episodes with long durations or psychotic features take a particular toll.

 Recovery, then, begins with prevention. Make sure patients understand this point by explaining that “each episode is like a small head injury, and the more episodes you have the worse these cognitive problems will get. Your brain needs time to heal, but it cannot do that if the episodes keep coming back.”

Next, set a reasonable goal in concrete terms. Engage patients by asking them “what would you most like to be able to do if these symptoms improved?” Cognitive remediation therapy improves functioning in bipolar disorder. Remarkably, it does so without bringing about meaningful improvements on objective tests of cognition. Instead, patients develop strategies to compensate for those deficits and implement their strategies in the real world. They learn to use calendars, to-do lists, reminders, and to break complex tasks into simpler steps.

 If rehabilitative therapists are not available, patients can borrow those techniques by setting goals and trouble-shooting their progress with the support of their clinician along the way (

Few treatments have been studied for cognitive symptoms of bipolar disorder, and most of what we know is borrowed from related disorders like schizophrenia and age-related cognitive decline. The general approach is to support the health of the brain and body, with the idea that good cognition flows from well-functioning metabolic, cardiovascular, and circadian systems. The 3 interventions with the 

 for cognition across various populations are aerobic exercise (45 minutes 3 to 5 times a week), diet (Mediterranean, Nordic, or Japanese style), and sleep.

If exercise is too difficult, start with a walk in the woods. Compared to a similar walk in an urban or suburban environment, walking in the woods for 60 to 90 minutes improved cognition in small studies of depression, attention-deficit/hyperactivity disorder (ADHD), and healthy college students.

To address dietary issues, start by introducing a few brain-friendly foods. Simple interventions like adding 1 to 2 daily servings of vegetables, nuts, or fruits (particularly blueberries) have improved cognition and mood in small controlled trials.

 With those in the mix, there is usually less room for the processed, fried, sugary, and fast foods that harm cognition.

Sleep consolidates memory and improves attention, processing speed, and creative problem solving. Unfortunately, sleep does not come easily to individuals with bipolar disorder, and trying to force it is counterproductive. Instead, patients should intervene at the points of the circadian cycle that are within their control (

). In clinical studies, nocturnal darkness helped stabilize mania independent of sleep, and in animal studies it enhanced learning and memory.

 can help but they are less effective than the previous strategies. Puzzles and word games have mild benefits that do not clearly translate into functional change. Some of the best-studied games for mild cognitive impairment are dexterity and so-called “exergames,” such as Wii Bowling. These movement-oriented games further 

 the importance of physical activity for cognitive health.

Bipolar disorder is associated with several medical conditions that can impair cognition, such as obesity, diabetes, cardiovascular disease, and sleep apnea. In the case of diabetes, there is evidence that both metformin and liraglutide improve cognition in mood disorders.

 Herpes simplex virus-1 is associated with worse cognition in bipolar disorder. In a small randomized, double-blind, placebo- controlled trial, valacyclovir improved cognition in this population even in the absence of genital lesions.

Among the mood stabilizers, lamotrigine has the most favorable cognitive profile. It improved cognition in large open-label studies and a post-hoc analysis of controlled trials.

 On the other hand, lamotrigine can cause word-finding problems, particularly in the elderly or when the dose goes above 150 mg/day.

Lithium has cognitive risks and benefits. Although most mood stabilizers have neuroprotective effects, the ones seen with lithium are broader, and there is evidence from 5 controlled trials that lithium 

 dementia in the lower dose range (serum levels of 0.25 to 0.5 mEq/L).

 On the other hand, small impairments in short-term memory and creativity were attributable to lithium in a meta-analysis of clinical data.

Well-designed trials of lithium’s cognitive effects are few, but 1 study looked at cognitive outcomes in 61 patients who were randomized to either lithium or quetiapine after a first-episode mania.

 After a year, those on lithium had greater verbal fluency than those on quetiapine. To test this in practice, ask the patient to name as many unique words as possible that start with the letter “P” in 1 minute.

Although some studies have found that atypical antipsychotics impair cognition, 1 small but well-designed 

 tells a different tale for lurasidone. This study included patients with bipolar disorder who were euthymic but experiencing cognitive problems. The participants were randomized to either open-label lurasidone (average dose 48 mg/day) or treatment as usual. After 6 weeks, the lurasidone-treated patients performed significantly better on a battery of cognitive tests compared to the treatment-as-usual group, with a large effect size of 0.8.

Valproate and carbamazepine are associated with deficits of attention, short-term memory, learning, and motor speed.

 There is no evidence that cognition improves on these 2 anticonvulsants. Furthermore, their cognitive profile was worse than that of lithium or lamotrigine in a naturalistic study.

Overall, mood stabilizers cause small but real cognitive impairments. Lamotrigine, lithium, and lurasidone may improve cognition in some ways and worsen it in others. These responses differ by patient, and the best way to manage them is to fine-tune the dose and change the mood stabilizer when necessary.

Patients with mood disorders often think that their cognitive problems are due to ADHD. About 15% of individuals with bipolar disorder have comorbid ADHD. However, if the symptoms began in adulthood and worsened with the mood episodes, it is unlikely that ADHD is the problem. In practice, this is difficult to tease apart, but some signs may lead the way. ADHD tends to make patients more hyped-up, with restless energy and prominent distractibility. The speech of patients with ADHD is marked by a frenetic, choppy rhythm, and they change topics frequently (even when not hypomanic). In comparison, the cognitive deficits of bipolar disorder have a slower feel and resemble age-related cognitive decline. Words do not come easily, and sentences are short. Forgetfulness, inertia, and indecision predominate.

 have calming effects on patients with ADHD because they treat the hyperactivity. In contrast, patients with bipolar disorder are more likely to feel energized on stimulants. At best, stimulants improve cognitive symptoms associated with bipolar disorder for 6 to 12 months and then tolerance sets in. At worst, they cause mania, mixed states, and psychosis. When genuine ADHD and bipolar disorder coexist, modafinil, armodafinil, clonidine, and guanfacine are safer alternatives. Atomoxetine, which resembles a noradrenergic antidepressant, is not a good alternative.

Besides the previously discussed mood stabilizers, there are few controlled pharmacotherapy trials for the cognitive symptoms of bipolar disorder. Treatments for dementia have failed (donepezil and galantamine), as have pramipexole, n-acetylcysteine, and methylene blue. Although modafinil and armodafinil have not been tested for cognitive symptoms of bipolar disorder, these agents 

 in other populations and have positive effects in bipolar depression.

A positive finding comes from an extract of the ashwagandha plant. This extract improved memory, reaction time, and social 

 in a randomized placebo-controlled trial of patients with bipolar disorder who were euthymic but had cognitive problems (n = 53; effect sizes, 0.26 to 0.62). Unfortunately, this trial has not been replicated, but it is backed by bench studies that found ashwagandha had neuroprotective effects on the hippocampus. The extract is readily available in products with “Sensoril” on the label (target dose, 500 mg/d; starting dose, 250 mg/d for the first week).

Bipolar disorder is defined by its symptoms, but it is the impairment that makes it an illness. Its symptoms, after all, are also part of normal life: elation, sadness, irritability, fatigue, and elevated energy. For many patients, the most painful part of bipolar disorder is the loss of control over their own mind. Most would rather lose control of their right arm than the things that define their selfhood: how they act, what they say, and what they think and feel

Cognitive symptoms extend that loss of control beyond the episodes of mania and depression. Linda Logan, a talented woman who wrote about her struggles with bipolar disorder in a 

 that went viral, explained these deficits were a threat to her identity.

 Even after her mood was stabilized, she “lost my sense of competence ... Word retrieval was difficult and slow ... Clarity of thought, memory, and concentration had all left me. I was slowly fading away.” Logan’s advice to psychiatrists was to “ask about what parts of the self have vanished.”

is the mood disorders section editor for 

the editor in chief of The Carlat Psychiatry Report, and the director of the Mood Treatment Center. He has written several books on mood disorders, most recently 

The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for

Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression

2. Burdick KE, Millett CE, Bonnín CDM, et al. 

The international consortium investigating neurocognition in bipolar disorder (ICONIC-BD)

3. Torrent C, Bonnin Cdel M, Martínez-Arán A, et al. Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study. 

4. Serra MC, Dondero KR, Larkins D, et al. 

Healthy lifestyle and cognition: Interaction between diet and physical activity

5. Berman MG, Kross E, Krpan KM, et al. Interacting with nature improves cognition and affect for individuals with depression. 

6. Travica N, D’Cunha NM, Naumovski N, et al. The effect of blueberry interventions on cognitive performance and mood: a systematic review of randomized controlled trials. 

7. Conner TS, Brookie KL, Carr AC, et al. Let them eat fruit! The effect of fruit and vegetable consumption on psychological well-being in young adults: a randomized controlled trial. 

8. Ren M, Zhang H, Qi J, et al. An almond-based low carbohydrate diet improves depression and glycometabolism in patients with type 2 diabetes through modulating gut microbiota and glp-1: a randomized controlled trial. 

9. Harvey AG, Soehner AM, Kaplan KA, et al. 

Treating insomnia improves mood state, sleep, and functioning in bipolar disorder: a pilot randomized controlled trial

10. Bedrosian TA, Vaughn CA, Galan A, et al. Nocturnal light exposure impairs affective responses in a wavelength-dependent manner. 

11. Heo JY, Kim K, Fava M, et al. Effects of smartphone use with and without blue light at night in healthy adults: a randomized, double-blind, cross-over, placebo-controlled comparison. 

12. Henriksen TE, Skrede S, Fasmer OB, et al. Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial. 

13. Hill NT, Mowszowski L, Naismith SL, et al. 

Computerized cognitive training in older adults with mild cognitive impairment or dementia: a systematic review and meta-analysis

14. Guo M, Mi J, Jiang QM, et al. Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. 

15. Mansur RB, Ahmed J, Cha DS, et al. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: a pilot, open-label study. 

16. Jancin B. Valacyclovir improves cognition in bipolar patients. 

17. Khan A, Ginsberg LD, Asnis GM, et al. Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder. 

18. Daban C, Martínez-Arán A, Torrent C, et al. Cognitive functioning in bipolar patients receiving lamotrigine: preliminary results. 

19. Kaye NS, Graham J, Roberts J, et al. Effect of open-label lamotrigine as monotherapy and adjunctive therapy on the self-assessed cognitive function scores of patients with bipolar I disorder. 

20. Dell’Osso L, Del Grande C, Gesi C, et al. A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts. 

21. Forlenza OV, Radanovic M, Talib LL, Gattaz WF. 

Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomized clinical trial

22. Wingo AP, Wingo TS, Harvey PD, Baldessarini RJ. Effects of lithium on cognitive performance: a meta-analysis. 

23. Daglas R, Cotton SM, Allott K, et al. A single-blind, randomized controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: a 12-month follow-up study. 

24. Yatham LN, Mackala S, Basivireddy J, et al. 

Lurasidone versus treatment as usual for cognitive impairment in euthymic patients with bipolar I disorder: a randomized, open-label, pilot study

25. Dias VV, Balanzá-Martinez V, Soeiro-de-Souza MG, et al. Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview. 

26. Gualtieri CT, Johnson LG. Comparative neurocognitive effects of 5 psychotropic anticonvulsants and lithium. 

27. Nunez NA, Singh B, Romo-Nava F, et al. 

Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: a meta-analysis of randomized controlled trials

28. Chengappa KN, Bowie CR, Schlicht PJ, et al. Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. 

The problem with how we treat bipolar disorder

Articles

For many patients, the most painful part of bipolar disorder is the loss of control over their own mind. 

Cognition, Bipolar Disorder, and the Self

Top Medications for Alcohol Use Disorders with Depression

One medication stood out as the most effective in a meta-analysis of alcohol use disorders with depression, but few patients are taking it.

Top Medications for Alcohol Use Disorders With Depression

7 Mistakes in Treatment Resistant Depression

Raise the dose, augment, or switch? A new study suggests we may need to give antidepressants more time to be effective.


7 Mistakes in Treatment-Resistant Depression

 is Instructor in Clinical Psychiatry at the

Wake Forest University School of Medicine

in Winston-Salem, NC. He is Editor in Chief of

and Bipolar Disorder Section Co-Editor for

Videos

Dr Aiken gives tips to feel more connected to your patient and become more aware of their lives. 

Making Telemedicine Work

Drug interactions, discontinuation issues, adverse effects, and more. These are the problems that are often overlooked.

7 Common Mistakes With Antidepressants

There are many reasons why symptoms worsen in younger patients who are prescribed antidepressants. Five possible scenarios are discussed in this podcast.

You get an urgent call from the mother of a 12-year-old patient. Three weeks ago she started fluoxetine for depression, and now she seems even more depressed. She is emotionally reactive: irritable, tearful, or anxious over everyday hassles. She is agitated and her sleep is worse, but there are no clear-cut symptoms of mania. What do you do?

, Associate Professor of Psychiatry and Behavioral Sciences and Director of the 

Stanford Pediatric Mood Disorders Program

, describes how she approaches cases like these. I met her at the American Psychiatric Association meeting in San Francisco, where she released a 

 The book is a thoughtful synthesis of the diverse views on this subject. There are many reasons why younger patients get worse on antidepressants, and we need to keep an open mind to all possibilities including:

1. Age of the child. Children younger than 12 are more likely to worsen on antidepressants. A slow and careful titration is very important in this population.

2. Family history of bipolar disorder. While 1 in 10 children get worse on an antidepressant in the general population, those odds rise to 1 in 2 when the child has a parent or first-degree relative with bipolar disorder.

3. Subthreshold manic symptoms. These include patients who have symptoms of mania that are too few in number or too short in duration to count toward a full diagnosis of 

. While DSM-5 requires 4 days of hypomanic symptoms to meet the criteria for bipolar disorder, hypomania tends to be shorter in children and adolescents.

4. Personal and family history of antidepressant response. If other family members have taken antidepressants, ask them how they responded. Often children who get worse on antidepressants have family members who had a similar response.

5. Dose response. Carefully evaluate how the symptoms changed-getting better or worse-as the dose was raised or increased. Sometimes going slower resolves the problem.

Whether to stop the medication, lower the dose, or switch to a mood stabilizer depends on what is causing the problem. For more tips on this decision, listen to the full interview above.

Dr Aiken is Instructor in Clinical Psychiatry at the 

 in Winston-Salem, NC. He is Editor in Chief of 

Dr Aiken does not accept honoraria from pharmaceutical companies but receives royalties from W.W. Norton & Co. for a book he co-authored with James Phelps, MD, 

Clinical Handbook for the Diagnosis and Treatment of Pediatric Mood Disorders

Washington, DC: American Psychiatric Publishing; 2019.

This podcast was originally posted on June 19, 2019, and has since been updated. -Ed

Podcasts

There are many reasons symptoms worsen in younger patients who are prescribed antidepressants. Five possible scenarios are discussed in this podcast.

When Children Get Worse on Antidepressants: Activation or Bipolar?

Chris Aiken, MD, and Kellie Newsome, PMH-NP, discuss how to dose quetiapine for the treatment of bipolar disorder.

Dr Aikenis the Mood Disorders Section Editor for Psychiatric Times, the Editor in Chief of 

 His written several books on mood disorders, most recently 

with his co-host Kellie Newsome, PMH-NP. Dr Aiken does not accept honoraria from pharmaceutical companies but receives royalties from PESI for 



Kellie L. Newsome, PMH-NP, is the cohost of the 

 and is also a practicing Psychiatric Mental Health Nurse Practitioner in Winston Salem, NC, at the Mood Treatment Center. Raised in Tasmania, Australia, Kellie moved to the United States in 1998.

For more on this topic, see 

Top Mood Stabilizers for Bipolar Disorder

Chris Aiken, MD, and Kellie Newsome, PMH-NP, discuss best practices for dosing quetiapine for the treatment of bipolar disorder.

Dosing Tips for Bipolar Disorder: Quetiapine

Ten sleep specialists assessed widely accepted beliefs and here's what they found.