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Synopsis
Terminology
Diagnosis
Treatment
Complications and Prognosis
Screening and Prevention

Nov.01.2022

Recurrent Major Depressive Disorder With a Seasonal Pattern

Synopsis

Key Points

Recurrent major depressive disorder with a seasonal pattern is diagnosed in patients when symptoms of depression emerge at a particular time of year, usually in winter
Diagnosis is based on the recognition of major depressive episodes occurring at a specific time of the year, causing social or occupational impairment, with the presence of at least 5 of the following symptoms, necessarily including depressed/irritable mood or anhedonia: ^r1
- Depressed mood or irritability for most of the day, and nearly every day, indicated via subjective report of the patient or via observation of others
- Anhedonia
- Sleep disturbance
- Change in weight or appetite
- Psychomotor retardation or agitation
- Fatigue or loss of energy
- Feelings of worthlessness or excessive or inappropriate guilt
- Diminished ability to concentrate or indecisiveness
- Recurrent thoughts of death, suicidal ideation, suicide attempt, or a specific plan for committing suicide
Must be differentiated from hypothyroidism, major depressive disorder, bipolar disorders I and II, cyclothymic disorder, and substance misuse
Principal treatment modalities consist of light therapy, cognitive behavioral therapy, and selective serotonin reuptake inhibitors
- These treatment options can be used in concert as well as individually
- In the case of fall/winter seasonality, light therapy is useful not only for treatment, but also as a prevention modality if begun in early fall

Urgent Action

Recognition of suicidal or homicidal ideation is urgent; when present, this warrants immediate referral to a psychiatrist and admission to psychiatric unit

Pitfalls

Failure to recognize the seasonality element of the condition can result in misdiagnosis (eg, cyclothymic disorder), leading to failure to implement effective treatment
Failure to recognize a patient’s suicidal or homicidal risk can lead to tragic consequences of an otherwise manageable condition

Terminology

Clinical Clarification

Recurrent major depressive disorder with a seasonal pattern is a major depressive disorder with a regular temporal relationship between symptomatic episodes and a particular time of the year ^r2

Classification

DSM-5 TR considers seasonality as an episode specifier for recurrent major depressive disorder ^r1
- Defining characteristic is the onset and remission of episodes of major depressive disorder at characteristic times of the year (usually beginning in fall or winter) ^r1
- Major depressive disorder ^r1
  - At least 5 of the following symptoms are present nearly every day during the same 2-week period:
    - Depressed mood most of the day
    - Markedly reduced interest or pleasure in all or nearly all activities
    - Change in appetite or weight (increase or decrease)
    - Sleep disturbance (insomnia or hypersomnia)
    - Psychomotor agitation or retardation (observable by others)
    - Fatigue or lack of energy
    - Reduced ability to think or concentrate; indecisiveness
    - Feelings of worthlessness or excessive, inappropriate guilt
    - Recurrent thoughts of death or suicidal ideation or attempt
  - Symptoms represent a change from usual functioning
  - At least 1 of the symptoms is depressed mood or loss of interest or pleasure
  - Symptoms cause clinically significant distress or impairment in social, work, or other areas of functioning
  - Episode is not attributable to the physiologic effects of substance use or other medical disorder
- Seasonal specifier ^r1
  - Depressive episodes must occur during a particular time of the year with predictable annual recurrence ^r3
  - This pattern of onset and remission of episodes must have occurred during at least a 2-year period (ie, 2 depressive episodes must have occurred in the previous 2 years) with no nonseasonal episodes occurring during this period
  - Seasonal major depressive episodes substantially outnumber the nonseasonal major depressive episodes that may have occurred during individual's life
  - The seasonal specifier does not apply to when the pattern is better explained by seasonally linked psychosocial stressors (eg, seasonal unemployment)
Recurrent major depressive disorder with a seasonal pattern can be further classified into 2 subtypes, based on the time of year in which episodes occur ^r2
- Winter or fall/winter recurrence
  - Accounts for the vast majority of cases, especially in populations living at high latitudes
  - Certain ethnic groups who live at very high latitudes and their descendants may have adapted to long winters and therefore are less prone
- Summer or spring/summer recurrence
  - Constitutes only a minority of cases ^r4
A subsyndromal type of seasonal depression, manifesting mostly with sleep disturbances, has been reported among individuals staying at Arctic and Antarctic sites ^r5

Diagnosis

Clinical Presentation

History

Seasonal pattern of symptoms ^r6
Any of the following symptoms or complaints are common:
- Decline in performance at work or school ^c1^c2
- Change in sleep, appetite, or weight (gaining or losing more than 5% body weight within a month, as reported by patient or observed by others) ^r1^c3^c4^c5
  - Hypersomnia with hyperphagia, craving for carbohydrates, and weight gain is typical of recurrent major depressive disorder with fall/winter seasonal pattern, as if patient were in a quasi-hibernation state ^r1^c6^c7^c8
  - Opposite symptom profile is typical of spring/summer pattern (ie, patient sleeps less, eats less, loses weight) ^c9^c10^c11
  - Seasonal specifier does not apply to those situations in which the pattern is better explained by seasonally linked psychosocial stressors (eg, seasonal unemployment or school schedule)
- Fatigue ^c12
- Loss of interest in sexual activity ^c13
- Headache or other pain ^c14^c15
- Concentration difficulty, indecisiveness, or memory impairment ^c16^c17^c18
- Nausea ^c19
- Change in bowel habits (constipation or diarrhea) ^c20^c21^c22
- Craving for carbohydrates ^c23
- Difficulty with morning awakening ^c24
Additional symptoms that may be present include:
- Anxiety or worry ^c25^c26
- Suicidal ideation or thoughts of death ^c27
- Feelings of guilt or worthlessness ^c28^c29
- Preoccupation with physical discomfort ^c30
- Symptoms of psychosis (eg, delusions, hallucinations) ^c31^c32^c33

Physical examination

Physical findings can include:
- Weight changes or, in the case of children, not meeting expected weight gain ^c34
- Signs of self-abuse (eg, scars, bruises, lacerations) ^c35^c36^c37^c38
Psychiatric signs
- Any of the following types of abnormal affect:
  - Blunted (flat) or constricted ^c39^c40
  - Irritable ^c41
  - Labile ^c42
  - Inappropriate ^c43
- Abnormal psychomotor activity is often seen
  - Psychomotor retardation ^c44
    - Indicated by slowed or absent spontaneous movement ^c45
    - Typical of the fall/winter pattern
  - Psychomotor agitation ^c46
    - Patient appears restless

Causes and Risk Factors

Causes

Condition is thought to be caused by combination of factors that likely include: ^r7
- Circadian phase delay or advance, probably affecting depressive symptoms via changes in melatonin levels ^c47
- Self prescribed medications that can be ineffective and/or cause side effects (such as melatonin) ^r8^c48
- Abnormal retinal sensitivity to light ^c49
- Neurotransmitter dysfunction ^c50
- Genetic variations affecting circadian rhythms ^c51
- Abnormal serotonin levels ^c52

Risk factors and/or associations

Age

Higher risk from age 18 to 30 years ^r9^c53
Younger people are at higher risk for winter depressive episodes than older people ^r1^c54

Sex

More common in women, with reported female to male ratio of 4 to 1 ^r7^c55^c56

Genetics

Variants of the melanopsin gene (OPN4) could predispose some individuals ^r10^c57
Having a first-degree relative who has experienced depressive symptoms increases the risk ^r9^c58

Other risk factors/associations

Residence at mid to high latitudes ^r11^c59
Severe visual impairment ^r12^c60
Chronic tinnitus ^r13^c61

Diagnostic Procedures

Primary diagnostic tools

History and physical examination ^r7^c62
Depression scales, inventories, and questionnaires ^r7
- Hamilton Depression Rating Scale and Beck Depression Inventory are commonly used ^c63^c64

Laboratory

Laboratory tests play no role in diagnosing the condition, but are used to rule out common conditions, such as substance abuse (urine screen for drugs of abuse) and hypothyroidism (TSH and thyroxine levels) ^r1^c65

Other diagnostic tools

Hamilton Depression Rating Scale ^r14^c66
- Recurrent major depressive disorder with a seasonal pattern is designated seasonal affective disorder on this scale
- Completed by examiner while observing patient
Beck Depression Inventory ^r15^c67
- Questionnaire answered by patient
- Available in standard 21-question format, or as an abridged 7-question format appropriate for screening in the primary care setting
- Elucidates severity, intensity, and depth of typical major depression symptoms

Differential Diagnosis

Most common

Hypothyroidism ^c68^d1
- Disorder characterized by inadequate synthesis and secretion of thyroid hormones ^r16
- Similarities ^r16
  - Patient has low energy or fatigue and may have depressed mood
  - Hypophagia
  - Weight gain
  - Hypersomnia
- Differences
  - TSH level is elevated ^r16
  - Free thyroid hormones (especially free thyroxine) are decreased ^r16
  - Usually there is no seasonal pattern or predictable annual occurrence, although seasonal course with summertime improvement has been seen with hypothyroidism ^r7
- Definitive diagnosis is made via thyroid panel (TSH and thyroxine levels) ^r16
Major depressive disorder without a seasonal pattern ^r1^c69^d2
- Major depressive disorder is defined by following symptoms, least 5 of which are present nearly every day during the same 2-week period:
  - Depressed mood most of the day
  - Markedly reduced interest or pleasure in all or nearly all activities
  - Change in appetite or weight (increase or decrease)
  - Sleep disturbance (insomnia or hypersomnia)
  - Psychomotor agitation or retardation (observable by others)
  - Fatigue or lack of energy
  - Reduced ability to think or concentrate; indecisiveness
  - Feelings of worthlessness or excessive, inappropriate guilt
  - Recurrent thoughts of death or suicidal ideation or attempt
- Symptoms represent a change from usual functioning and cause clinically significant distress or impairment in social, work, or other areas
- At least 1 of the symptoms is depressed mood or loss of interest or pleasure
- Similar to recurrent major depressive disorder with a seasonal pattern in the history of major depressive episodes defined by presence of 5 or more of the same features; different in that there is no seasonal pattern or predictable annual occurrence
- Diagnosis is entirely clinical, based mostly on history
Bipolar disorder ^r1^c70^d3
- Mood disorder characterized by cycling between depressive and manic or hypomanic episodes
  - Bipolar I disorder
    - Criteria have been met for at least 1 manic episode in patient's lifetime
    - Manic episode may have been preceded by or followed by hypomanic or major depressive episodes
    - Occurrence of the manic and major depressive episode(s) cannot be better explained by schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or other schizophrenia spectrum or psychotic disorders
  - Bipolar II disorder
    - Criteria have been met for at least 1 hypomanic episode and at least 1 major depressive episode in patient's lifetime
    - No history of manic episodes
    - Occurrence of the hypomanic and major depressive episode(s) cannot be better explained by schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or other schizophrenia spectrum or psychotic disorders
    - Depressive symptoms or unpredictability caused by frequent alternation between periods of hypomania and depression causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
- Similar to recurrent major depressive disorder with a seasonal pattern in that patient meets criteria for at least 1 major depressive episode; different in that there is no seasonal pattern or predictable annual occurrence
- Diagnosis is entirely clinical, based mostly on history
Cyclothymic disorder ^r17^c71
- Characterized by mood cycling that does not meet diagnostic criteria for major depressive disorder or bipolar disorders I or II
- Similar to recurrent major depressive disorder with a seasonal pattern in that major depressive disorder symptoms come and go; different in that there is no seasonal pattern or predictable annual occurrence
- Diagnosis is entirely clinical, based mostly on history
Substance-related disorder ^r18^c72
- Condition resulting from misuse of alcohol or drugs
- Similar to recurrent major depressive disorder with a seasonal pattern in that both can manifest with changes in mood, social and occupational impairment, and other similar symptoms
- Different in that use of a substance can be identified and established via admission by patient, observation of others, or medical tests (eg, urine screening for drugs of abuse)
- Definitive diagnosis is based on history, physical examination, and appropriate substance abuse work-up, which includes:
  - Questioning regarding quantity of alcohol consumed and/or types and quantities of drugs used
  - Assays on urine samples for alcohol, opioids, benzodiazepines, cocaine/stimulants, cannabis, and other drugs of abuse
- After a positive screening test result, conversation with patient is focused on the substance use to elicit DSM-5 symptoms of a substance use disorder, which include:
  - Tolerance
  - Withdrawal
  - Using more drugs than intended
  - Failed efforts to cut down or quit
  - Spending a lot of time related to use
  - Craving
  - Failure to fulfill important life roles
  - Giving up important life activities
  - Use in hazardous situations
  - Continued use in spite of either negative physical/psychological problems, or social/interpersonal consequences

Treatment

Goals

Abatement of depression symptoms
Recognition of any suicidal or homicidal potential ^r6
Identification and management of medical complications of depression, such as malnutrition and nonadherence to medical treatment
Return of patient to normal social/occupational activities and function
Prevention of recurrent episodes

Disposition

Admission criteria

Admission to an inpatient psychiatric unit is warranted when patient cannot care for self or is a danger to self or others, owing to either of the following: ^r19
- Suicidal or homicidal ideation
  - Previous suicide attempts or violence can strengthen the case for admission when case is equivocal
- Presence of psychotic symptoms

Recommendations for specialist referral

Consult psychiatrist for any of the following:
- Suicidal or homicidal ideation or attempts
- Alcohol or drug dependence or misuse
- Comorbid psychosis, suspected bipolar disorder, or personality or developmental disorders
- Dementia, delirium, or confusion
- Lack of response to light therapy

Treatment Options

Principal treatment modalities consist of the following:

Light therapy (also called bright light therapy) ^r20
- Primary treatment modality
Cognitive behavioral therapy ^r21
- Efficacy is comparable with light therapy
- Acceptable treatment option; may have prophylactic benefits for subsequent years
Second generation antidepressant drugs, especially selective serotonergic reuptake inhibitors ^r22
- Second line treatment
- Some evidence, albeit limited in quality and quantity, shows effectiveness for fluoxetine and sertraline ^r22
  - Light therapy and fluoxetine are comparably effective and well tolerated; other clinical factors, such as patient preference, might guide the selection of treatment ^r22

Drug therapy

Selective serotonin reuptake inhibitors ^r9^c73
- Bupropion (extended-release bupropion hydrochloride tablets; e.g., Wellbutrin XL): ^r23^c74
  - Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]; Adults: Initiate in the autumn with 150 mg PO once daily in the AM; titrate after 7 days to target dose of 300 mg PO once daily in the AM. Continue through winter, then taper and discontinue in early spring. Individualize regimen to patient's historical pattern of SAD episodes. For those receiving 300 mg/day, taper to 150 mg/day prior to discontinuation. Total daily doses above 300 mg/day were not evaluated in SAD clinical trials.
- Fluoxetine ^r9^c75
  - Fluoxetine Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: 20 mg PO once daily, initially. May increase dose after several weeks if insufficient clinical improvement is observed. May divide doses of 20 mg/day or more in 2 doses. Max: 80 mg/day.
- Sertraline ^r9^c76
  - Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose by 25 to 50 mg/day at intervals of at least 1 week as needed. Usual dose: 50 to 200 mg/day. Max: 200 mg/day.

Nondrug and supportive care

The following nondrug therapies have been used to treat this condition: ^r7

Light therapy
Cognitive behavioral therapy

Procedures

Light therapy ^r20^c77

General explanation

Just after awakening, patient is positioned next to a special light-emitting device to receive 5000 lux hours per day
- Usually, this is achieved using a 10,000 lux device for 30 minutes
- Patient can engage in any activity while receiving treatment, but must keep eyes within the needed distance from the light source as indicated by the instructions for the particular device
- Abatement of major depressive symptoms within a few weeks (usually within 2 weeks) indicates that treatment is effective

Indication

Recurrent major depressive disorder with fall/winter seasonal pattern

Contraindications

Patients with bipolar disorder receiving light therapy are at greater risk of developing manic or hypomanic episodes; however, light therapy is not a contraindication for these patients

Psychological therapy can include counseling or mindfulness based cognitive therapy ^r24^c78

General explanation

Mindfulness based cognitive therapy is highly structured, focused, short-term, and therapist-patient collaborative; consists of the following principal components:
- Functional analysis
  - Patients are taught to recognize irrational thoughts and assumptions, and irrational connections between assumptions, thoughts, and behaviors that underlie, exacerbate, and perpetuate depression
  - Patients are taught to track, stop, and redirect thoughts with the aim of different behaviors, thereby changing the emotional response that underlies the depression
- Skills training
  - Patients are taught to unlearn behaviors that underlie and exacerbate depression and to learn new behaviors via a variety of techniques, including:
    - Exposure and desensitization
    - Learning exercises and home assignments
    - Adoption of pleasurable activities during the problematic time of the year
Generally, cognitive behavioral therapy shows results in a few weeks or a few months; resolution of depressive symptoms within that time period suggests the treatment has been effective

Indication

Recurrent major depressive disorder with seasonal pattern in any of the following scenarios:
- Light therapy is inadequate in abating symptoms
- Patient refuses light therapy or is not adherent
- Light therapy is not appropriate, owing to nonwinter seasonality of the recurrent depression
- Patient is eager to begin cognitive behavioral therapy alongside light therapy

Comorbidities

Major psychiatric disorders ^c79
- Bipolar disorders I and II ^c80^c81^d3
  - Typically require additional treatment alongside light therapy or cognitive behavioral therapy
- Cyclothymic disorders ^c82
  - Patients can have a seasonal element (treatable with light therapy) plus depressive features throughout the year, requiring continuous psychotherapy or medication
- Anxiety disorders, including obsessive-compulsive disorder ^c83^c84
  - May alter the plan for any cognitive behavioral therapy, requiring it to be longer or more intense
- Eating disorders ^c85
  - Can exacerbate or hide the changes in appetite of recurrent major depressive disorder with a seasonal pattern, thereby making the diagnosis more challenging
- Depression during pregnancy or the postpartum period ^c86^c87^d4
  - Symptoms of depression are common in the postpartum period, and this period may correlate with the season during which a patient with recurrent depressive disorder suffers symptoms ^d5
  - Cognitive behavioral therapy may be the best first option; effects of light therapy during pregnancy are largely unknown
  - Selective serotonin reuptake inhibitors entail a treatment dilemma: some data show neurobehavioral and long-term cognitive problems among children of women who were treated with those drugs during pregnancy, but untreated maternal depression also carries serious risks for both mother and child
Personality and developmental disorders ^c88^c89^d6
- May alter the plan for any cognitive behavioral therapy, requiring it to be longer or more intense
- In the case of certain personality disorders, such as borderline personality disorder, presence as a comorbid condition may require dialectic behavioral therapy ^d6
  - Dialectic behavioral therapy is a modified form of cognitive behavioral therapy that is focused on changing behaviors that are particularly common in borderline personality disorder (eg, suicidal ideation, self-harm, substance misuse)

Monitoring

Schedule patients for regular follow-up and use a standardized scale to measure response to therapy, as this has been shown to improve outcomes ^r25
- Hamilton Depression Rating Scale or Beck Depression Inventory are useful for monitoring, as are other standardized depression scales (eg, the Patient Health Questionnaire [PHQ-9])

Complications and Prognosis

Complications

Suicide ^r6^c90
Impaired social and occupational performance ^c91^c92
Disrupted interpersonal relations ^c93
Substance misuse ^c94

Prognosis

Response to light therapy within 2 weeks of initiation predicts a favorable outcome ^r14
A meta-analysis supported the efficacy of light therapy in both seasonal and nonseasonal depression, and reported effect sizes that were equivalent to those in most trials of antidepressants ^r26
Improvement of atypical symptoms (eg, hypersomnolence, increased appetite, carbohydrate craving) after 1 hour of light therapy correlates with improvement of disorder after 2 weeks of therapy ^r14

Screening and Prevention

Screening ^c95

Prevention

Consider initiating light therapy in early fall for patients with fall/winter seasonality ^r7^c96
- Evidence supporting light therapy for prevention is limited owing to small studies and methodologic flaws; requires discussion with patient ^r3
Bupropion is the only medication shown to be effective in preventing recurrence of seasonal affective disorder, but adverse effects, such as headaches, nausea, and insomnia, are commonly observed ^r9
Lifestyle adjustments are recommended by some experts, including: ^r7^c97
- Exercising more often ^c98
- Increasing light in the home ^c99
- Practicing relaxation and stress management techniques ^c100^c101
- Spending more time outside ^c102
- Visiting sunnier, warmer climates ^c103

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