Affective disorders, sleep patterns, and treatment implications

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’t understand what causes depression, or how antidepressant treatments work
The bipolar spectrum
Identified 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);
Depression with flight of ideas: “In a usual picture of depression, inhibition of thought may be replaced by flight of ideas…They cannot hold fast their thoughts at all; constantly things come crowding into their heads….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”.
Excited depression: “extraordinary poverty of thought but, on the other hand, great restlessness…mood is anxious, despondent, lachrymose, irritable, occasionally mixed with a certain self-irony”
Depressive-anxious mania: “a morbid state…composed of flight of ideas, excitement, and anxiety…mood is anxiously despairing.” Ideas of sin and persecution or hypochondriacal delusions are frequently present (2)
Unproductive mania
Inhibited mania
Manic stupor
What we think of as major depression is classified as a manic-depressive type of psychosis
Does 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).
There are no mixed states defined for Bipolar II disorder.
Mixed state – more relaxed definition
A 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%.
Depressive mixed states
In 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).
Feeling dysphoric = feeling sad, depressed, hopeless, irritable, down, fearful, worried, discouraged, worthless (Winokur)
Dysphoria was found in 5-73% of bipolar outpatients, depending on the definition used (3).
A 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).
Another 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)
A 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:
Overt expression of irritability
At least two associated symptoms from the following list:
1. expressed (subjective) internal tension
2. expressed (subjective) irritability or feeling of hostility
3. aggressive or destructive behaviour
4. suspiciousness
Symptoms are present for at least 24 h

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).

Agitated depression
Has 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:
Major depressive episode
At least 2 of the following symptoms:
1. Motor agitation
2. Psychic agitation or intense inner tension
3. Racing or crowded thoughts.
Unipolar depression: risk for bipolar illness
A 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).
Bipolar disorder in the elderly
Most elderly patients with bipolar disorder present with a mixture of depressive and manic symptoms (10).
Suicidal risk
54.5% of 44 patients with mixed episodes were suicidal compared to 2% of 49 manic patients (11).
Lithium vs valproate
Pure mania responds better to lithium, but the presence of even one depressive symptom during mania favors a response to valproate over lithium (12)

Pure depression
Mixed states
Pure mania

Racing; flight of ideas

Euphoric OR irritable
Psychomotor activity


Thought content

Inflated self-esteem

High (11)

Pleasurable activities
Loss of interest

Excessive involvement
Decreased or increased

Energy level

Excessive (either insomnia or hypersomnia)

Decreased need
Time in bed
Increased (eg, late rising)

Social rhythms
Delayed morning activities(13)

Sleep EEG
Reduced REM latency
Increased REM density
Decreased delta sleep

Disrupted social rhythms (14).
Insomnia (15)

Sleep deprivation (16)
Changes in social rhythms (eg Ramadan for Muslim patients) (17)

Effective treatments
Reduce REM sleep:
Most antidepressants (18, 19)
Sleep deprivation
ECT (20)
Exercise (21)
Psychostimulants (22)
Increase SWS, eg trazodone (23), olanzapine (24)
Lamotrigine (reduces REM sleep (25))
Alprazolam (26, 27)
Increase sleep:
Sedating antipsychotics
Delay circadian rhythms: lithium (28)
Stabilize circadian rhythms: lithium, carbamazepine, verapamil (29)
Social rhythms therapy (30)
Treatments requiring caution
Antidepressants without a mood stabiliser (may trigger mania, rapid cycling)
Sleep deprivation (may trigger mania; risk about same as with antidepressants (31))

Other issues:
What 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’ve slept well. Olanzapine simultaneously decreases REM sleep and increases delta sleep. Trazodone also increases delta sleep.
How 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.

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