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Letter to the Editor

Treatment Strategies for Bipolar Disorder: CALM SEA

Roger Sparhawk, MD, and S. Nassir Ghaemi, MD, MPH

Published: May 19, 2011

Treatment Strategies for Bipolar Disorder: CALM SEA

To the Editor: A prior shorter mnemonic (CALM, published previously in the Companion1) helped clinicians organize the pharmacologic treatment options for bipolar disorder. The current mnemonic CALM SEA incorporates a review of biorhythm and endocrine issues, as well as an image of the goal.

C = Control Cycling, starting with manic and mixed symptoms, especially insomnia, irritability, agitation, impulsivity, and anxiety, as these disrupt work situations and social supports (burn bridges), and even subsyndromal mixed mania has been associated with increased risk for suicidal behavior.2,3 Uncontrolled cycling renders patients’ lives chaotic, unpredictable, and unmanageable.

A = Antidepressants. Use conventional antidepressants (preferential unipolar antidepressants4) sparingly and selectively beyond 10 weeks. Adjunctive antidepressants have demonstrated benefit beyond 10 weeks of treatment in only 15% to 20% of bipolar patients, and only in the Stanley Foundation Bipolar Network studies.4-8 Two important recent Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) studies9,10 showed no separation of adjunctive antidepressants from adjunctive placebo. Further, another STEP-BD study with 1,742 patients followed for up to 1 year showed that “patients who received antidepressants were 3.8 times as likely to experience rapid cycling,” ie, 4 or more mood episodes (P = .001), and “2.0 times as likely to have 2 or 3 episodes (P = .0001) . . . compared to patients who did not receive antidepressants.”11(p374) For longer term use, consider preferential bipolar antidepressants,4 eg, lamotrigine, quetiapine, lithium, or olanzapine,4,12 with appropriate monitoring.

L = Longitudinal/long-term view. A longitudinal/long-term view of mood episodes over months to years is pivotal to making the diagnosis of bipolar disorder in the first place, to understanding the patient’s intrinsic or baseline pattern of mood cycling, and to accurately gauging the patient’s response to treatment.

M = Mood stabilizers, especially lithium, divalproex, and carbamazepine, remain the core building blocks of effective bipolar disorder regimens.13 Lamotrigine provides an extremely helpful floor against recurrent depression but lacks robust antimanic coverage.4,14

S = Sleep. Consistent, regular-onset, full-duration, uninterrupted, restorative sleep is an essential component of any recovery from bipolar disorder and can generally be reestablished using primarily the sedative and antimanic properties of lithium, divalproex, or carbamazepine, with or without atypical antipsychotics. Antidepressants may aggravate insomnia,15 and gradual antidepressant taper over months often relieves it.16,17

E = Endocrine/metabolic hot spots can be remembered
as TSH:

TThyroid augmentation may relieve cycling or depression18,19 with even mild hypothyroidism, or even euthyroid state. Monitor TSH periodically, especially in lithium-treated patients.

SSteroid treatments may trigger mood episodes, usually mania or mixed states.

HHormonal shifts (especially in women), such as puberty/menarche, postpartum, and perimenopause/menopause, may initiate mood episodes.

A = Activity. Regular activity, exercise, and social activity, including “‘ social zeitgebers,’ ie, persons, social demands, or tasks that set the biological clock,”20(p948) comprise the important complement of regular sleep in maintaining a regular sleep-wake cycle and “lifestyle regularity,”21 indispensable components of recovery.20-22 Therefore, it may be advantageous to explain this to patients and their family or support system so that they can structure activity and social interaction as part of their recovery.


1. Sparhawk R, Ghaemi SN. CALM: a mnemonic for treatment options for bipolar disorder. Prim Care Companion J Clin Psychiatry. 2008;10(6):485-486. PubMed doi:10.4088/PCC.v10n0612f

2. Goldberg JF, Garno JL, Leon AC, et al. Association of recurrent suicidal ideation with nonremission from acute mixed mania. Am J Psychiatry. 1998;155(12):1753-1755. PubMed

3. Sato T, Bottlender R, Tanabe A, et al. Cincinnati criteria for mixed mania and suicidality in patients with acute mania. Compr Psychiatry. 2004;45(1):62-69. PubMed doi:10.1016/S0010-440X(03)00145-7

4. Sparhawk R. Treatment of mood disorders: a surprising omission, and the role of lamotrigine as a prototypical bipolar antidepressant. Prim Psychiatry. 2010;17(7):17-19.

5. Altshuler LL, Suppes T, Black D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry. 2003;160(7):1252-1262. PubMed doi:10.1176/appi.ajp.160.7.1252

6. Altshuler LL, Post RM, Hellemann G, et al. Impact of antidepressant continuation after acute positive or partial treatment response for bipolar depression: a blinded, randomized study. J Clin Psychiatry. 2009;70(4):450-457. PubMed doi:10.4088/JCP.08m04191

7. Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163(2):232-239. PubMed doi:10.1176/appi.ajp.163.2.232

8. Post RM, Leverich GS, Nolen WA, et al; Stanley Foundation Bipolar Network. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord. 2003;5(6):396-406. PubMed doi:10.1046/j.1399-5618.2003.00065.x

9. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711-1722. PubMed doi:10.1056/NEJMoa064135

10. Ghaemi SN, Ostacher MM, El-Mallakh RS, et al. Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety. J Clin Psychiatry. 2010;71(4):372-380. PubMed doi:10.4088/JCP.08m04909gre

11. Schneck CD, Miklowitz DJ, Miyahara S, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008;165(3):370-377, quiz 410. PubMed doi:10.1176/appi.ajp.2007.05081484

12. Sachs GS. Managing Bipolar Affective Disorder. London, UK: Science Press. Bipolar Depression Pathway; 2004:49-53.

13. Goldberg JF, Brooks JO 3rd, Kurita K, et al. Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: findings from the STEP-BD. J Clin Psychiatry. 2009;70(2):155-162. PubMed doi:10.4088/JCP.08m04301

14. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry. 2009;194(1):4-9. PubMed doi:10.1192/bjp.bp.107.048504

15. Stahl SM. Stahl’s Essential Psychopharmacology. 3rd ed. Cambridge, UK: Cambridge University Press; 2008:531.

16. Ghaemi SN. Bipolar disorder and antidepressants: an ongoing controversy. Prim Psychiatry. 2001;8(2):28-34.

17. Mostert M, Dubovsky SL. When bipolar treatment fails, what’s your next step? Current Psychiatry. 2008;7(1):39-46.

18. Post RM, Leverich GS. Thyroid augmentation. In: Treatment of Bipolar Illness: A Casebook for Clinicians and Patients. New York, NY. WW Norton and Co; 2008:415-422.

19. Frye MA, Yatham L, Ketter TA, et al. Depressive relapse during lithium treatment associated with increased serum thyroid-stimulating hormone: results from two placebo-controlled bipolar I maintenance studies. Acta Psychiatr Scand. 2009;120(1):10-13. PubMed doi:10.1111/j.1600-0447.2008.01343.x

20. Ehlers CL, Frank E, Kupfer DJ. Social zeitgebers and biological rhythms: a unified approach to understanding the etiology of depression. Arch Gen Psychiatry. 1988;45(10):948-952. PubMed

21. Frank E, Hlastala S, Ritenour A, et al. Inducing lifestyle regularity in recovering bipolar disorder patients: results from the maintenance therapies in bipolar disorder protocol. Biol Psychiatry. 1997;41(12):1165-1173. PubMed doi:10.1016/S0006-3223(96)00241-7

22. Frank E, Kupfer DJ, Thase ME, et al. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Arch Gen Psychiatry. 2005;62(9):996-1004. PubMed doi:10.1001/archpsyc.62.9.996

Roger Sparhawk, MD

S. Nassir Ghaemi, MD, MPH

Author affiliations: Department of Psychiatry, St Thomas Hospital, Summa Health System, Akron, and Northeast Ohio Universities College of Medicine, Rootstown (Dr Sparhawk); and Tufts University School of Medicine, Mood Disorders Program, Tufts Medical Center, Boston, Massachusetts (Dr Ghaemi).

Potential conflicts of interest: Dr Sparhawk has in the past served as a speaker for and/or consultant to AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Otsuka, Pfizer, and Wyeth and as a clinical investigator for AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Janssen, Neurocrine, Sepracor, and Wyeth. Neither Dr Sparhawk nor his family hold equity positions in pharmaceutical companies. Dr Ghaemi has served as a consultant to Sepracor and has received grant/research support from Pfizer.

Funding/support: None reported.

Published online: May 19, 2011 (doi:10.4088/PCC.10l01106).

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