Problem issues in treatment of affective disorders
\nOnly 60-70% of depressed patients respond to antidepressants (in carefully done studies). The clinical reality is worse.
\nIn some patients, antidepressants worsen agitation, may increase suicidality
\nWe still don\u2019t understand what causes depression, or how antidepressant treatments work
\nThe bipolar spectrum
\nKraepelin
\nIdentified pure depressive episodes, pure manic episodes, and 6 subtypes of mixed states, depending on the polarity of three elements: thought disorder, mood, and psychomotor activity (1);
\nDepression with flight of ideas: \u201cIn a usual picture of depression, inhibition of thought may be replaced by flight of ideas\u2026They cannot hold fast their thoughts at all; constantly things come crowding into their heads\u2026.in such cases we have to do with the appearance of a flight of ideas which only on account ot the inhibition of external movements of speech is not recognisable. The patient are almost mute and are rigid in their whole conduct and are of cast-down and hopeless mood\u201d.
\nExcited depression: \u201cextraordinary poverty of thought but, on the other hand, great restlessness\u2026mood is anxious, despondent, lachrymose, irritable, occasionally mixed with a certain self-irony\u201d
\nDepressive-anxious mania: \u201ca morbid state\u2026composed of flight of ideas, excitement, and anxiety\u2026mood is anxiously despairing.\u201d Ideas of sin and persecution or hypochondriacal delusions are frequently present (2)
\nUnproductive mania
\nInhibited mania
\nManic stupor
\nICD9
\nWhat we think of as major depression is classified as a manic-depressive type of psychosis
\nDSM-IV
\nDoes not include depressive mixed states (ie, major depressive episodes with some hypomanic symptoms); also does not include manic episodes with less than syndromal depression, even though both of these are probably more common than DSM-IV mixed episode (meeting criteria for both MDE and manic episode) only 5-8% in a study of 37 outpatients with bipolar disorder (3).
\nThere are no mixed states defined for Bipolar II disorder.
\nMixed state \u2013 more relaxed definition
\nA full manic episode, with 3 out of 9 depressive symptoms which can reliably be distinguished from manic symptoms: depressed mood, markedly diminished interest or pleasure, substantial weight gain or increased appetite, hypersomnia, psychomotor retardation, fatigue or loss of energy, feelings of worthlessness, feelings of helplessness or hopelessness, recurrent thoughts of death (4). Using this definition, the number of mixed state cases in a series of 71 manic patients increased from 34% (using strict DSM-IIIR criteria) to 40%.
\nDepressive mixed states
\nIn a series of 70 consecutive bipolar II and unipolar depressed outpatients, 90% had at least one hypomanic symptom, and 28.5% had 3 or more symptoms (eg irritable mood, distractibility, racing thoughts, increased talking) (5).
\nDysphoria
\nFeeling dysphoric = feeling sad, depressed, hopeless, irritable, down, fearful, worried, discouraged, worthless (Winokur)
\nDysphoria was found in 5-73% of bipolar outpatients, depending on the definition used (3).
\nA study of 105 inpatients meeting RDC and DSM-IIIR criteria for manic episodes were rated using 37 behavioral rating items from the Schedule for Affective Disorders and Schizophrenia. Cluster analysis suggest that manic episodes can be classified as classic (predominately euphoric), dysphoric, or depressed (6).
\nAnother study of 237 inpatients with DSM-IIIR bipolar disorder, manic (n=204) or mixed (n=33) were rated. Five symptom factors were identified. The strongest factor represented dysphoria in mania, with strong positive loadings for depressed mood, lability, guilt, anxiety, and suicidal thoughts and behaviours, and strong negative loading for euphoric mood (7)
\nA recent article suggests a new way to classify mixed states, by adding to the depressive and manic syndrome the concept of dysphoria as a third dimension (8). Dysphoria would have the following criteria:
\nOvert expression of irritability
\nAt least two associated symptoms from the following list:
\n1. expressed (subjective) internal tension
\n2. expressed (subjective) irritability or feeling of hostility
\n3. aggressive or destructive behaviour
\n4. suspiciousness
\nSymptoms are present for at least 24 h<\/p>\n
We thus have pure depression, dysphoric depression, pure mania, dysphoric mania, type I mixed state (corresponds to DSM-IV mixed state) either with or without dysphoria, and two other states, IID (full major depressive episode, with at least one manic symptom and dysphoria), and IIM (full manic episode, with at least 3 depressive symptoms and dysphoria).<\/p>\n
Agitated depression
\nHas lost its status as a mixed state, partially because ECT is effective for both agitated and retarded depressions (2). Was considered a subtype of major depression in the RDC, but has not been carried over into DSM-IIIR or DSM-IV. Thus, the disease entity melancholia became the syndrome agitated depression which then became a symptom, agitation, of a depressive episode. Unfortunately, treatment with antidepressants often leads to worsening: more agitation, insomnia, anxiety, and suicidal ideas (2). These authors suggest that agitated depression is really a mixed state, and should be labelled as mixed depression, with these diagnostic criteria:
\nMajor depressive episode
\nAt least 2 of the following symptoms:
\n1. Motor agitation
\n2. Psychic agitation or intense inner tension
\n3. Racing or crowded thoughts.
\nUnipolar depression: risk for bipolar illness
\nA fifteen-year prospective followup study of 74 patients initially hospitalized for unipolar major depression: 27% developed one or more periods of hypomania; 19% full bipolar I mania (9).
\nBipolar disorder in the elderly
\nMost elderly patients with bipolar disorder present with a mixture of depressive and manic symptoms (10).
\nSuicidal risk
\n54.5% of 44 patients with mixed episodes were suicidal compared to 2% of 49 manic patients (11).
\nTreatment
\nLithium vs valproate
\nPure mania responds better to lithium, but the presence of even one depressive symptom during mania favors a response to valproate over lithium (12)<\/p>\n
Pure depression
\nMixed states
\nPure mania
\nThought
\nSlowed<\/p>\n
Racing; flight of ideas
\nMood
\nDepressed<\/p>\n
Euphoric OR irritable
\nPsychomotor activity
\nDecreased<\/p>\n
Increased
\nSpeech
\nSlowed<\/p>\n
Pressured
\nThought content
\nPoverty
\nWorthlessness
\nGuilt
\nHypochondriasis<\/p>\n
Inflated self-esteem
\nGrandiosity
\nParanoia
\nSuicidality<\/p>\n
High (11)<\/p>\n
Pleasurable activities
\nLoss of interest<\/p>\n
Excessive involvement
\nAppetite
\nDecreased or increased<\/p>\n
Energy level
\nFatigued<\/p>\n
Excessive
\nSleep
\nExcessive (either insomnia or hypersomnia)<\/p>\n
Decreased need
\nTime in bed
\nIncreased (eg, late rising)<\/p>\n
Decreased
\nSocial rhythms
\nDelayed morning activities(13)<\/p>\n
Sleep EEG
\nReduced REM latency
\nIncreased REM density
\nDecreased delta sleep<\/p>\n
Triggers
\nDisrupted social rhythms (14).
\nInsomnia (15)<\/p>\n
Sleep deprivation (16)
\nStimulants
\nAntidepressants
\nChanges in social rhythms (eg Ramadan for Muslim patients) (17)<\/p>\n
Effective treatments
\nReduce REM sleep:\u2028Most antidepressants (18, 19)
\nSleep deprivation
\nECT (20)
\nExercise (21)
\nPsychostimulants (22)
\nIncrease SWS, eg trazodone (23), olanzapine (24)
\nLamotrigine (reduces REM sleep (25))
\nAlprazolam (26, 27)
\nIncrease sleep:\u2028Anticonvulsants\u2028Benzodiazepines\u2028Sedating antipsychotics
\nDelay circadian rhythms: lithium (28)
\nStabilize circadian rhythms: lithium, carbamazepine, verapamil (29)
\nSocial rhythms therapy (30)
\nTreatments requiring caution
\nAntidepressants without a mood stabiliser (may trigger mania, rapid cycling)
\nSleep deprivation (may trigger mania; risk about same as with antidepressants (31))<\/p>\n
Other issues:
\nWhat is the role of delta sleep in these disorders? Delta sleep increases with length of time awake, and is the component of sleep associated with feeling rested. Individuals who obtain more delta sleep are more likely to get out of bed early because they feel they\u2019ve slept well. Olanzapine simultaneously decreases REM sleep and increases delta sleep. Trazodone also increases delta sleep.
\nHow is CBT effective in treating a biologic illness? One possibility is that by encouraging the patient to go on with life, eg return to work or school, get out of the house, etc. the patient will as a side effect get up earlier (less REM sleep) stay awake longer (ie no long naps) which will increase delta sleep and stimulate earlier rising.<\/p>\n
1. Freeman MP, McElroy SL. Clinical picture and etiologic models of mixed states. Psychiatr Clin North Am 1999;22(3):535-46, vii.
\n2. Koukopoulos A, Koukopoulos A. Agitated depression as a mixed state and the problem of melancholia. Psychiatr Clin North Am 1999;22(3):547-64.
\n3. Bauer MS, Whybrow PC, Gyulai L, Gonnel J, Yeh HS. Testing definitions of dysphoric mania and hypomania: prevalence, clinical characteristics and inter-episode stability. J Affect Disord 1994;32(3):201-11.
\n4. McElroy SL, Strakowski SM, Keck PE, Jr., Tugrul KL, West SA, Lonczak HS. Differences and similarities in mixed and pure mania. Compr Psychiatry 1995;36(3):187-94.
\n5. Benazzi F. Major depressive episodes with hypomanic symptoms are common among depressed outpatients. Compr Psychiatry 2001;42(2):139-43.
\n6. Dilsaver SC, Chen YR, Shoaib AM, Swann AC. Phenomenology of mania: evidence for distinct depressed, dysphoric, and euphoric presentations. Am J Psychiatry 1999;156(3):426-30.
\n7. Cassidy F, Forest K, Murry E, Carroll BJ. A factor analysis of the signs and symptoms of mania. Arch Gen Psychiatry 1998;55(1):27-32.
\n8. Dayer A, Aubry JM, Roth L, Ducrey S, Bertschy G. A theoretical reappraisal of mixed states: dysphoria as a third dimension. Bipolar Disord 2000;2(4):316-24.
\n9. Goldberg JF, Harrow M, Whiteside JE. Risk for bipolar illness in patients initially hospitalized for unipolar depression. Am J Psychiatry 2001;158(8):1265-70.
\n10. Cohen RE, Tueth MJ, Lenox RH. Manic behavior in the elderly. Clin Geriatrics 1999;7(6).
\n11. Dilsaver SC, Chen YW, Swann AC, Shoaib AM, Krajewski KJ. Suicidality in patients with pure and depressive mania. Am J Psychiatry 1994;151(9):1312-5.
\n12. Swann AC, Bowden CL, Morris D, Calabrese JR, Petty F, Small J, et al. Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry 1997;54(1):37-42.
\n13. Ashman SB, Monk TH, Kupfer DJ, Clark CH, Myers FS, Frank E, et al. Relationship between social rhythms and mood in patients with rapid cycling bipolar disorder. Psychiatry Res 1999;86(1):1-8.
\n14. 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):948-52.
\n15. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? [see comments]. 1989;262(11):1479-84.
\n16. Wehr TA. Sleep-loss as a possible mediator of diverse causes of mania. 1991;159:576-8.
\n17. Kadri N, Mouchtaq N, Hakkou F, Moussaoui D. Relapses in bipolar patients: changes in social rhythm? Int J Neuropsychopharmacol 2000;3(1):45-49.
\n18. Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. 1997;58(8):348-50.
\n19. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, See WR. Sleep laboratory studies on the single-dose effects of serotonin reuptake inhibitors paroxetine and fluoxetine on human sleep and awakening qualities. Sleep 1991;14(5):439-47.
\n20. Cohen HB, Dement WC. Sleep: suppression of rapid eye movement phase in the cat after electroconvulsive shock. 1966;154(747):396-8.
\n21. Driver HS, Meintjes AF, Rogers GG, Shapiro CM. Submaximal exercise effects on sleep patterns in young women before and after an aerobic training programme. Acta Physiologica Scandinavica. Supplementum 1988;574:8-13.
\n22. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, Barbanoj MJ. Differential effects of a new central adrenergic agonist–modafinil– and D-amphetamine on sleep and early morning behaviour in young healthy volunteers. 1989;9(3):183-95.
\n23. Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Gruber G, Mandl M, Strobl R, et al. Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry 2002;26(2):249-60.
\n24. Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo. Biol Psychiatry 2000;47(5):468-70.
\n25. Placidi F, Diomedi M, Scalise A, Marciani MG, Romigi A, Gigli GL. Effect of anticonvulsants on nocturnal sleep in epilepsy. 2000;54(5 Suppl 1):S25-32.
\n26. Gilbert A, Hendrie HC. Treatment of agitated depression with alprazolam. Am J Psychiatry 1987;144(5):688.
\n27. Kahn JP, Stevenson E, Topol P, Klein DF. Agitated depression, alprazolam, and panic anxiety. Am J Psychiatry 1986;143(9):1172-3.
\n28. Lenox RH, Gould TD, Manji HK. Endophenotypes in bipolar disorder. Am J Med Genet 2002;114(4):391-406.
\n29. Klemfuss H, Kripke DF. Antimanic drugs stabilize hamster circadian rhythms. Psychiatry Res 1995;57(3):215-22.
\n30. Frank E, Swartz HA, Kupfer DJ. Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder. Biol Psychiatry 2000;48(6):593-604.
\n31. Riemann D, Voderholzer U, Berger M. Sleep and sleep-wake manipulations in bipolar depression. Neuropsychobiology 2002;45 Suppl 1:7-12.<\/p>\n","protected":false},"excerpt":{"rendered":"
Affective Disorders, Sleep Patterns, and Treatment Implications Problem issues in treatment of affective disorders Only 60-70% of depressed patients respond to antidepressants (in carefully done studies). The clinical reality is worse. In some patients, antidepressants worsen agitation, may increase suicidality We still don\u2019t understand what causes depression, or how antidepressant… <\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[89],"tags":[13,94,11],"class_list":["post-73","post","type-post","status-publish","format-standard","hentry","category-medicine","tag-depression","tag-ritalin","tag-sleep"],"_links":{"self":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/73","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=73"}],"version-history":[{"count":5,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/73\/revisions"}],"predecessor-version":[{"id":1110,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/73\/revisions\/1110"}],"wp:attachment":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=73"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=73"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=73"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}