Depression

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

Original Editors - Nadine Risman from Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

Depression is defined according to Goodman and Fuller as a morbid sadness, dejection, or a sense of melancholy distinguished from grief.  Depression falls under the broader category of Major Depressive Disorders which are characterized by a single isolated episode lasting weeks to months.  Major depressive disorders are viewed as an adjustment disorder which occurs due to external circumstances such as stress, trauma or loss.  Other major depressive disorders include dysthymia and seasonal affective disorder. 

Prevalence

Depression is the most commonly seen mood disorder within a therapy practice and is often associated with other physical illnesses and psychological conditions.  In 2006, the Center for Disease Control conducted a study looking at the prevalence of depression.  They found that approximately 15.7% of people reported being told by a health care provider that they had depression at some point in their lifetime.¹  Men and women ages 25 to 44 have the highest occurance of depression with the elderly population being the next highest age group affected. 

Characteristics/Clinical Presentation

It is important to note that as many as one third of people experiencing depression do not feel sad or blue.  Many experience somatic symptoms such as fatigue, joint pain, headaches, gastrointestinal disturbances, or chronic back pain.  In Goodman and Synder, they report that 80 to 90% of the most common gastrointestinal disorders are associated with depressive or anxiety disorders.  People with depression commonly have trouble sleeping, including early morning and frequent nocturnal awakenings.  In the elderly population, sleep disturbances are the first symptom of depression especially when linked with acute confusion, falling, bowel and bladder problems or syncope.  Clinical signs and symptoms can include:

• Persistent sadness, low mood, or feelings of emptiness
• Frequent or unexplained crying spells
• A sense of hopelessness
• Feelings of quilts or worthlessness
• Problems in sleeping
• Loss of interest or pleasure in ordinary activities or loss of libido
• Fatigue or decreased energy
• Appetite loss (or overeating)
• Difficulty in concentrating, remembering, and making decisions
• Irritability
• Persistant joint pain (arthralgia)
• Headache
• Chronic back pain
• Bilateral neurologic symptoms of unknown cause (e.g., numbness, dizziness, weakness)
• Thoughts of death or suicide
• Pacing and fidgeting
• Chest pain and palpitations

There may also be associated behavior changes that can include: compulsive, reckless or violent behavior, argumentative or oppositional behavior, patients may have a preoccupation with themselves, be critical toward family members (fault finding) or be unaffectionate with their partner or spouse.  Other somatic symptoms that are associated with mood disorders in nonmedicated people includes:

• Muscle Pain (myalgia)
• Excess Perspiration
• Dry Mouth or Excessive Salivation
• Rapid Breathing
• Blurred Vision
• Constipation
• Tinnitus
• Dry Skin
• Flushing
• Slurred Speech
• Amenorrhea, Polymenorrhea
• Digestive Problems

Associated Co-morbidities

Patients with these disorders are at higher risk for developing depression due to the disease pathology or medications associated with treating these disorders.

Medications

Depression may be caused by medications a patient is taking to treat another medical problem.  Sedatives, hypnotics, cardiac drugs, antihypertensives, anticonvulsants, hormones and steriods are some drug catergories that can cause depression.  Also recreational drugs such as alcohol and illegal drugs can cause signs and symptoms of depression.  Some examples are as follows:

Psychoactive Agents: Amphetamines, Cocaine, Benzodiazepines, Barbiturates, Neuroleptics

Antihypertensive Drugs: Beta Blockers (especially propranolol), Alpha Adrenergic Antagonists, Methyldopa (Aldomet), Hydralazine (Apresoline)

Analgesics: Salicylates, Propoxyphene (Darvocet-N), Pentazocine (Talwin), Morphine, Meperidine (Demerol)

Cardiovascular Drugs: Digoxin (Lanoxin), Procainamide (Pronestyl), Disopyramide (Norpace)

Anticonvulsants: Phenytoin (Dilantin), Phenobarbital

Hormonal Agents: Corticosteroids, Oral Contraceptives, Anabolic Steroids

Miscellaneous: Alcohol, Illicit Drugs, Histamine H₂ Receptor Antagonists (especially cimetidine or Tagamet), Metoclopramide (Reglan), Levodopa (Dopar, Larodopa), Nonsteroidal Antiinflammatory Drugs (NSAIDs), Antineoplastic Agents (Vinblastine), Disulfiram (Antabuse), Cytokines (Interferons)

Diagnostic Tests/Lab Tests/Lab Values

Depression is often under diagnosed by primary care physicians due to patients complaining of somatic pain rather than feelings of sadness.  Physians tend to treat the somatic issues first through medication.  Also the criteria in the DSM-IV makes diagnosing depression difficult because many patients don't fit the diagnostic criteria.  Under the current DSM version the diagnosic criteria for a single episode of Major Depressive Disorder is:

• A. Presence of a single Major Depressive Episode
• B. The Major Depressive Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
• C. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode.

Note: This exclusion does not apply if all of the manic-like, mixed-like, or hypomanic-like episodes are substance or treatment induced or are due to the direct physiological effects of a general medical condition.

If the full criteria are currently met for a Major Depressive Episode, specify its current clinical status and/or features:

Mild, Moderate, Severe without Psychotic Features/Severe with Psychotic Features, Chronic, with Catatonic Features, with Melancholic Features, with Atypical Features, with Postpartum Onset

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Dysthymic Disorder is a mild chronic depression that is characterized by more cognitive issues like low self esteem and hopelessness rather than problems with sleep or appetite.  Many times those who have had a major depressive episode suffer from dysthymic disorder.  Dysthymic is diagnosed on the following criteria listed in the DSM-IV.

• A. Depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.
• B. Presence, while depressed, of two (or more) of the following:

        1. Poor appetite or overeating

        2. Insomnia or hypersomnia

        3. Low energy or fatigue

        4. Low self-esteem

        5. Poor concentration or difficulty making decisions

        6. Feelings of hopelessness

• C. During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more than 2 months at a time.
• D. No Major Depressive Episode has been present during the first 2 years of the disturbance (1 year for children and adolescents); i.e., the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, In Partial Remission.

Note: There may have been a previous Major Depressive Episode provided there was a full remission (no significant signs or symptoms for 2 months) before development of the Dysthymic Disorder. In addition, after the initial 2 years (1 year in children or adolescents) of Dysthymic Disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are met for a Major Depressive Episode.

• E. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode, and criteria have never been met for Cyclothymic Disorder.
• F. The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder.
• G. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
• H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

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In the DSM-IV there is another category listed for the diagonosis of depressive disorders that do not meet the criteria of the other mood disorders. It is important to note that the psychosocial distress or dysfunction experienced must not be due to the physiological effects of a substance or a general medical condition.  The Depressive Disorder Not Otherwise Specified category includes disorders with depressive features that do not meet the criteria for Major Depressive Disorder, Dysthymic Disorder, Adjustment Disorder With Depressed Mood, or Adjustment Disorder With Mixed Anxiety and Depressed Mood . 

Sometimes depressive symptoms can present as part of an Anxiety Disorder Not Otherwise Specified. Examples of Depressive Disorder Not Otherwise Specified include:

• 1. Premenstrual dysphoric disorder: in most menstrual cycles during the past year, symptoms (e.g., markedly depressed mood, marked anxiety, marked affective lability, decreased interest in activities) regularly occurred during the last week of the luteal phase (and remitted within a few days of the onset of menses). These symptoms must be severe enough to markedly interfere with work, school, or usual activities and be entirely absent for at least 1 week postmenses.
• 2. Minor depressive disorder: episodes of at least 2 weeks of depressive symptoms but with fewer than the five items required for Major Depressive Disorder.
• 3. Recurrent brief depressive disorder: depressive episodes lasting from 2 days up to 2 weeks, occurring at least once a month for 12 months (not associated with the menstrual cycle).
• 4. Postpsychotic depressive disorder of Schizophrenia: a Major Depressive Episode that occurs during the residual phase of Schizophrenia.
• 5. A Major Depressive Episode superimposed on Delusional Disorder, Psychotic Disorder Not Otherwise Specified, or the active phase of Schizophrenia.
• 6. Situations in which the clinician has concluded that a depressive disorder is present but is unable to determine whether it is primary, due to a general medical condition, or substance induced.

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There are also several questionnaires that can be used to help determine if a patient is at risk for developing or has depression.  The results of the questionnaire can help direct a patients referral to more qualified health care professionals.  The following are a few examples of depression questionnaires.

The Beck Depression Inventory Second Edition: 21 item self-report form that is intended to assess the existance and severity of symptoms of depression in adilts and adolescents 13 year and older.  The patient should answer the questions based on how they have felt for the last 2 weeks.  There is a version of this test that can be used for medical patients that is a seven item self-report measure of depression in adolescents and adults that reflects the cognitive and affective symptoms of depression while excluding somatic and perfomrnace symptoms that might be attributable to other conditions.  When scoring the Beck the higher the score the higher the feelings of depression are.  All of the Beck Scales have been validated in assisting health care professionals in making focused and reliable client evaluations.

Geriatric Depression Scale (short form): 15 question self-report form that the patient answers based off how they have felt over the last week.  Each question is worth one point and scores higher than 5 suggest depression and scores above 10 almost always indicate depression.

Zung Depression Scale: 20 question self-report form that the patient answers based off how often the statement describes how they have felt in the last several days.  Each question is scored on a scale of 1 to 4 with higher scores indicating more feelings of depression.

Causes

There are several theories on why depression occurs based on biochemical mechanisms, neuroendocrine mechanisms, sleep abnormalities, genetics and psychosocial factors. 

Biochemical Mechanisms: an imbalance in the neurotransmitters norepinephrine and serotonin. Depression is caused when norepinephrine, dopamine and serotonin are produced in inadequate amounts or the receptor sites for these transmitters are not functioning properly. Excessive amounts of norepinephrine and dopamine results in a mania state commonly found in those with bipolar disorder.

Neuroendocrine Mechanisms: this results when there are abnormalities in the limbic hypothalamic-pituitart-adrenal (HPA) axis. There can be an over secretion of cortisol, suppressed nocturnal secretion of melatonin, and decreased prolactin production in response to tryptophan administration. There are also associations to some forms of depression when testosterone, follicle stimulating hormone and leuteinizing hormone levels are low. Knowing this information may result in a clinical lab test that can diagnose depression based off of low or high serum levels found in a blood test.

Sleep Abnormalities: sleep changes are consistantly associated with depression but there is some debate on whether sleep disturbances cause depression or if depression causes sleep disturbances. Those prone to depression will have decreased REM latency (the time between falling asleep and the first REM period), longer first REM period, less continuous sleep, and early morning awakenings.

Genetics: there does appear to be a genetic linkage of major depressive disorder in that it occurs up to three times more often in first degree biologic relatives of people with this disorder.

Psychosocial Factors: this includes things like major life events and percieved stress. While it is not clear if these things cause depression or are just a factor in determining those who are likely to develop depression. Often an episode of depression will follow a severe psychosocial stressor such as the death of a loved one. Also these types of stressors play a larger role in the first and second episodes of depression and a lesser role in a more chronic form of depression.

Medical Management (current best evidence)

The medical mangagement of depression revolves largely around the use of pharmacotherapy, psychosocial therapy and electroconvulsive therapy (ECT) also known as shock therapy.  ECT utilizes an electrical impulse sent to the brain producing a controlled seizure which then alters the concentration of neurotransmitters in the brain, producing an effect that is simliar to how antidepressants work.  This form of therapy is not used as much as a first choice of treatment but may be benefical to patients who are severely suicidal, self-mutilating, catatonic, or unable to eat or function.  ECT may be used as a last resort if a more conservative treatment of antidepressants and psychosocial therapy has failed to make improvements in the patients symptoms.  The most common treatment utilized first when treating patients with depression is through pharmacotherapy.

When treating depression using pharmacotherapy, all of the antidepressants drugs work based off the theory that depression occurs because of an imbalance of neurotransmitters in the brain.  Based off this idea, most antidepressants work in a similiar manner by blocking the reuptake of either serotonin or norepinephrine back into the presynaptic nerve.  This allows excess neurotransmitter to build up in the synaptic cleft between the nerves which in turn leads to a down-regulation of the postsynaptic receptors.  It is this down-regulation which is then theorized to relieve the symptoms of depression. There are two main categories of medications, Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors.

Tricyclic Antidepressants (TCAs):  This category of medications was orginally designed as an anitpsychotic drug but were found to be helpful only with reducing depression symptoms in those patients with schizpphrenia, but did not reduce psychosis.  TCAs work in a similiar manner described above in that they block the reuptake of serotonin and norepinephrine into the presynaptic nerve.  Some TCAs also block the reabsorption of dompamine by competing with binding sites.  Picking a TCA for treatment is based off how much sedatation is desired and the subsequent side effects.  Administration of TCAs to treat depression is 60% effective in relieving the symptoms of depression.  Because TCAs also bind to several different receptors in the brain which is then responsible for a variety of side effects including the following:

• dry mouth
• constipation
• urinary retention
• blurred visions
• tachycardia
• sedation
• weight gain
• orthostatic hypotension
• dizziness
• decreased libido
• abnormal ejaculation
• impotence
• prolongation of QT interval on ECG (arrhythmias)
• sudden death

These side effects tend to be more pronounced on the elderly.  The use of TCAs also make the effects of alcohol and other sedatives more profound.  TCAs have a very small toxic window, about 5 times the normal daily dose.  If an over dose occurs the patient may experience: metabolic acidosis, arrhythmias and condution deficits, tremors, delirium, and bowel and bladder paralysis.  Also complicating the situation is the long half life of TCAs making the patient at risk for cardiac events 3 or 4 days after an initial overdose.

Selective Serotonin Reuptake Inhibitors (SSRIs): This category of drug has revolutionized how doctors treat depression.  This was one of the first drugs that was developed to purposely effect only the serotonin receptors for the specific purpose of limiting serotonin reuptake.  This category of drugs do not bind to other neuroreceptors which then limits their side effects, especially cardiotoxic events.  Also SSRIs have a higher toxic window as compared to TCAs, althought the specific amount has yet to be determined.  SSRIs are indicated for use in patients with major depression but can also be sued to treat obsessive complusive disorder, social phobia, generalized anxiety disorder, panic disorder, posttraumatic stress disorder, premenstrual syndrome, and eating disorders.  SSRIs work by desensitizing the serotonin receptors in the brain, making them more receptive to serotonin molecules as well as blocking the reuptake of serotonin leading to a down regulation.  The half lives of SSRIs varies depending on the medication. Some drugs have a much longer half life, which is good for patients with low compliance to taking their medications but also then limits there ability to change medications.  Side effects can include:

• nausea
• anorexia
• weight loss
• bleeding
• erectile dysfunction
• delayed ejaculation in men
• anorgasmia in women
• antidiuretic syndrome resulting in hyponatremia (nervousness, agitation, depression)
• serotonin syndrome (change in mental state, restlessness, hyperreflexia, disphoresis, shivering, tremors)
• akathisia
• dystonia
• dyskinesia
• tardive dyskinesia, parkinsonism
• bruxism
• restlessness
• agitation
• anxiety
• headaches
• insomnia

Abrupt discontinuation of any antidepressant drug can result in withdrawal symptoms.  The most common withdrawal symptoms are GI related, flu-like symptoms, disequilbrium, extrapyramidal symptoms, anxiety, crying spells, irritability, confusion, and sleep disturbances.

Physical Therapy Management (current best evidence)

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Alternative/Holistic Management (current best evidence)

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Differential Diagnosis

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Case Reports

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Resources

Geriatric Depression Scale (Short Form)

http://www.stanford.edu/~yesavage/GDS.english.short.score.html

Beck Depression Inventory II

www.pearsonassessments.com/HAIWEB/Cultures/en-us/Productdetail.htm

Zung Depression Scale

healthnet.umassmed.edu/mhealth/ZungSelfRatedDepressionScale.pdf

Recent Related Research (from Pubmed)

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References

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