chap 14 - affective disorders

Question 1

mood disorders

Answer 1

Mood disorders include major depressive disorder, dysthymic disorder, and bipolar disorder.

Approximately 20.9 million American adults, or about 9.5 percent of the U.S. population age 18 and older each year, have a mood disorder.

Major depressive disorder is more prevalent in women than in men.

The median age of onset for mood disorders is 30 years.

Depressive disorders often co-occur with anxiety disorders and substance abuse.

Question 2

major depressive disorder

Answer 2

Sadness
Hopelessness
Despair
Anhedonia
Mental slowness
Fatigue or reduced motor activity
Reduced sexual behaviors
Weight change and reduced or increased hunger
Significant risk and thoughts of suicide

Question 3

diagnosis of major depressive disorder

Answer 3

five or more of the following symptoms that have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure
- depressed mood most of the day, nearly every day, as indivated by either subjective report or observations by others
- markedly diminished interest or pleasure in all, or almost all, activites, most of the day
- significant weight loss when not dieting or weight gain
- insomnia or hypersomnia
- psychomotor agitaion
- fatigue or loss of energy
- feelings of worthlessness
- diminished ability to think or concentrate
- recurrent thoughs of death

Question 4

suicide

Answer 4

In 2019:Suicide was the tenth leading cause of death overall in the United States, claiming the lives of over 47,500 people.

More than 90 percent of people who kill themselves have a diagnosable mental disorder, most commonly a depressive disorder or a substance abuse disorder.

The highest suicide rates in the U.S. are found in white men over age 85.

Four times as many men as women die by suicide; however, women attempt suicide two to three times as often as men.

Question 5

persistent depressive disorder

Answer 5

Symptoms of PDD (chronic, mild depression) must persist for at least two years in adults (one year in children) to meet criteria for the diagnosis.

PDD affects approximately 1.5 percent of the U.S. population age 18 and older each year. i.e., about 3.3 million American adults.

The median age of onset of PDD is 31.
- formerly known as dysthymia, is a mood disorder consisting of the same cognitive and physical problems as depression with less severe but longer-lasting symptoms

Question 6

bipolar (manic-depressive disorder)

Answer 6

• Bipolar disorder affects approximately 5.7 million American adults, or about 2.6 percent of the U.S. population age 18 and older in a given year.
• The median age of onset for bipolar disorders is 25 years
• Characterized by:
  - Mood swings- depression to mania
  
  • Euphoria
  • Elation
  • Restlessness
  • Hyperactivity
  • Insomnia

Question 7

physiological and biochemical signs in depression

Answer 7

Vegetative
- Increased heart rate
- Decreased heart rate variability
- Increased cardiovascular reactivity to psychosocial stressors
- Increased susceptibility to heart disease

Endocrine
- Increased plasma norepinephrine
- Increased cerebrospinal fluid CRF
- Increased plasma corticosterone
- Altered proinflammatory cytokines in depressed mood

Circadian
- Altered sleep cycles
- Increased REM
- Decreased REM onset latency
- Sleep deprivation and depression
- Altered CRF cycle
- Seasonal affective disorder

Question 8

average plasma cortisol concentrations

Answer 8

Average plasma cortisol concentrations measured every hour in 7 unipolar depressed patients and 54 control subjects. The normal reduction in plasma cortisol occurring in the early morning and in the evening is significantly blunted in depressed patients. P<0.05; **P<0.01; **P<0.001.

There is a clear connection between blood cortisol levels, sleep and depression.
Cortisol is a stress hormone and one of the most important regulators of the circadian (daily) rhythms of the body. A key feature of normal morning awakening is a surge in cortisol before getting up from bed and declining levels before going to bed. The blood cortisol levels of depressed people do not decline as they should (maximum levels are not significantly different from normal people’s maximal levels).

Question 9

the hypothalamic-pituitary-adrenal axis in depression

Answer 9

The hypothesis behind the Dex Suppresion test was that depressed patients have an abnormal hypothalamic-pituitary-adrenal axis.
(A) In response to stress, the HPA axis causes secretion of glucocorticoids, including cortisol. Cortisol feeds back to the brain to inhibit further release of CRH, ACTH and glucocorticoids (negative feedback). The negative feedback control of further secretion is important.

(B) Depressed people have elevated levels of cortisol compared to people with other psychiatric problems and normal controls.

(C) and (D) Patients with depression have an impaired response on the dexamethasone suppression test.

In normal people, dexamethasone should decrease plasma cortisol levels by lowering the hypothalamic production of corticotropin releasing factor by negative feedback, thereby reducing pituitary adrenocorticotropic hormone and the adrenal production of cortisol. The failure to suppress plasma cortisol was regarded as a biologic marker of major depression. However, the test has fallen from favor as it can’t differentiate people with depression from people who might have conditions such as congestive heart failure, hypertension, unstable diabetes mellitus, extreme weight loss, obesity, dementia, bereavement, and alcoholism.

Question 10

patterns of the stages of sleep of a normal subject and of a patient with major depression

Answer 10

Sleep disturbances are a characteristic symptom of mood disorders. This is an example of a disruption in sleep patterns involving REM sleep.
Usually, people with a severe mood disorder have little difficulty falling asleep, but they awaken early and are unable to bet back to sleep. Depressed patients tend to enter REM sleep sooner than normal people and spend an increased time in this state during the last half of sleep. When depressed patients are deprived of REM sleep by awakening them whenever the EEG showed signs that they were entering this stage the deprivation decreased their depression. However, it takes several sessions to feel the effect. These findings are supported by the observation that treatments that alleviate depression, such as electroconvulsive therapy and the tricyclic antidepressant drugs, profoundly reduce REM sleep in cats.

Details:
Note the reduced sleep latency, reduced REM latency, reduction in slow-wave sleep (stages 3 and 4), and general fragmentation of sleep (arrows) in the depressed patient.

Question 11

sleep and depression

Answer 11

• the latency for the onset of REM sleep is reduced in depressed patients
  -emphasizes the reduced latency of depressed people to enter REM sleep.
  Note that depressed people require far less time to enter REM sleep than normal people across all age groups.

Question 12

changes in the depression rating of a depressed patient produced by a single nights total sleep deprivation

Answer 12

Just as specific deprivation of REM sleep has an antidepressant effect, total sleep deprivation also has an antidepressant effect.
However, total sleep deprivation produces immediate effects—but the effects are short-lived. Total sleep deprivation works for about 2/3 of endogenously depressed patients. The mood is improved the next day, but when allowed to sleep normally the depression is back. It is suggested that a depressogenic substance is produced during sleep but disappears during waking.

It can be predicted which depressed people will benefit from sleep deprivation. It depends on their circadian pattern of mood. Most people feel better at a particular time of day– generally, either the morning or the evening. Depressed people also show these fluctuations in mood. Depressed people who were most likely to show an improvement in mood after a night of total sleep deprivation were those who felt worst in the morning and best in the evening. Maybe these people are most sensitive to the hypothetical depressogenic substance produced during sleep? This substance makes them feel worst in the morning, and as the day progresses, the chemical is metabolize and they start feeling better. A night without sleep simply prolongs this improvement in mood.

Depression can sometimes be alleviated by changing sleep habits. The idea is to treat the depressed patient like someone who is having trouble adjusting to a change in time zones. One method is to have the person go to sleep earlier than usual. Sometimes the result is a relief from depression that lasts for months.
Another approach is to keep the person awake all night. This produces a rapid relief from depression but the benefits last only a day or two and depressed patients hate to go through this treatment.

Question 13

seasonal affective disorder

Answer 13

• Distinctive constellation of symptoms including
  
  • Overeating
  • Oversleeping
  • Carbohydrate craving
• Triggered by light deficiency
• Responds to phototherapyThis is not a case of “holiday blues”, referring to the Thanksgiving through New Year’s season, as people in the Southern hemisphere have these symptoms 6 months out of phase with people in the Northern hemisphere.

SAD is characterized by symptoms of depression like depressed mood, loss of libido and inability to concentrate or focus attention but also has a distinct constellation of symptoms not found in depression: overeating with excessive weight gain, oversleeping, and carbohydrate cravings.

The suggestion is that there is a disruption to normal circadian rhythms due to insufficient entrainment with light in the shorter winter months. People sometimes benefit from “light therapy”.

Question 14

light box therapy in SAD

Answer 14

• Individuals suffering from SAD can sometimes obtain relief using daily light therapy, whereby they sit in front of a light box for 1-2 hours early each morning during the autumn and winter. Light boxes produce bright illumination (>2500 lux), which is thought to help resynchronize biological rhythms.
  -Individual (solid circles) and average (horizontal bars) ratings of mood on the Hamilton rating scale for either individuals with SAD at baseline and after morning (a.m.), evening (p.m.), or combined (a.m. + p.m.) light treatment. Light treatment that took place during the morning resulted in significantly improved mood (that is, lower depression scores) as compared with baseline mood or evening treatment.

Question 15

depression and comorbidity with other disorders

Answer 15

High Comorbidity with:
- Psychological disorders, e.g., anxiety disorders
- Drug abuse
- Physiological disorders, e.g., heart failure; various cancers
- Comorbidity is the rule with depressive and anxiety disorders. As a rule of thumb many psychiatrists assume comorbid depression and anxiety until proven otherwise. Mood disorders, including depression and bipolar disorders, are the most common psychiatric comorbidities among patients with substance use disorders.
- Compared with the general population, depression is up to five times more common in heart failure patients. Depression affects approximately 15% to 25% of cancer patients.

Question 16

theories of depression

Answer 16

monoamine, macrophage/cytokine theory, stress

Question 17

monoamine hypothesis

Answer 17

states that depression is caused by the underactivity in the brain of monoamines, such as dopamine, serotonin, and norepinephrine.
-The monoamine theory, proposed in 1965, suggests that depression results from functionally deficient monoaminergic (norepinephrine and/or 5-HT) transmission in the CNS.
The theory was based on the ability of known antidepressant drugs (TCA and MAOI) to facilitate monoaminergic transmission, and of drugs such as reserpine to cause depression.
Other pharmacological evidence fails to support the monoamine hypothesis.
Biochemical studies on depressed patients do not, in general, support the monoamine hypothesis, except that consistently low concentrations of 5-HIAA in the CSF are found.
Though the monoamine hypothesis in its simple form is no longer tenable as an explanation of depression, pharmacological manipulation of monoamine transmission remains the most successful therapeutic approach.
-Reduced neurotransmission at 5-HT and NE synapses is largely responsible. This notion was supported by the finding that drugs that increased transmission (by preventing reuptake) improved mood.

Question 18

macrophage theory

Answer 18

states that inflammation causes macrophages to release pro-inflammatory cytokines which have CNS effects on brain monoamine systems

Question 19

chronic stress

Answer 19

decreases the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus causing cells to die.

Question 20

stahl’s hypothesis

Answer 20

Norepinephrine Deficiency Syndrome
Depressed mood
Impaired attention
Problems concentrating
Deficiencies in working memory
Slowness of information processing
Psychomotor retardation
Fatigue
Serotonin Deficiency Syndrome
Depressed mood
Anxiety
Panic
Phobia
Obsessions and compulsions
Food craving; bulimia

Question 21

chronic stress and depression

Answer 21

Chronic stress causes neuronal atrophy: a decreased number of spine synapses. Basic research studies demonstrate that repeated stress causes atrophy of neurons in the prefrontal cortex and hippocampus of rodents. Shown on the left is a diagram of a segment of a dendrite that is decorated with spines, and the reduction in spine number after exposure to repeated stress. On the right are examples of two photon laser microscopy images of neurobiotin-labeled dendrites from layer V pyramidal neurons in the prefrontal cortex of rats housed under control conditions or after exposure to immobilization stress (7 days, 45 minutes per day).

Question 22

the course of an acute infection

Answer 22

The physiological state induced by pathogens referred to as sickness and the behaviors that accompany sickness is referred to as “sickness behavior.” Sicknes behavior is triggered by the proinflammatory cytokines produced by activated cells of the innate immune system*. These cytokines include mainly interleukin (IL) 1 (IL-1α and IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Sickness behavior usually is terminated by endogenous anti-inflammatory molecules. Many of the symptoms that accompany sickness are the same that accompany depression.

Question 23

sickness behavior

Answer 23

Proponents: B.L. Hart,bR. Dantzer & K.W. Kelly
Sickness Symptoms
* Weakness
* Malaise
* Listlessness
* Unable to concentrate
Sickness Behaviors
* Anorexia
* Hypersomnia
* Reduced social contacts
* Depressed activity
Sickness and Sickness Behavior
* Cause and effect
Fever
* Adaptive utility (M. Kluger)
Fever-Sickness Behavior Hypothesis: Interleukin 1 (IL 1)
* Endogenous pyrogen
* Acts on brain
-  fever
-  feeding
-  SWS
* Route of access to brain

Question 24

lines of support for the macrophage/cytokine theory

Answer 24

Lines of Support

1.     Volunteers given monokines (IL-1; INF-; TNF) develop symptoms of
          a major depressive episode.

2.	IL-1 can account for hormonal abnormalities (e.g.,  ACTH;  GH).

3.	Diseases and cohorts characterized by macrophage activation are
           associated with high rates of depression.

4.	Brain macrophages (microglia) secrete monokines.

5.	Estrogen increases IL-1 secretion by macrophages.

6.	Eicosapentaenoic acid suppresses macrophages, whereas linoleic
           acid activates them.

7.	Substantial epidemiology is consistent with this hypothesis.

Question 25

cytokine actions in the brain

Answer 25

alter brain neurochemical systems and produce depression
-Cytokines can cause all the symptoms and signs of at least two mental illnesses: depression and schizophrenia.
Cytokines have powerful effects on neurotransmitter activities, including those linked with depression and schizophrenia, such as norepinephrine, serotonin and dopamine. However, this theory of depression works for only some subset of people who become depressed.

In response to tissue damage, macrophages release pro-inflammatory cytokines which have CNS effects (likely reducing DA and 5-HT). Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation.

TLR = Toll-like receptors (TLRs), a class of proteins that play a key role in the innate immune system.

Question 26

stress and the interaction of the HPA and immune system cytokines

Answer 26

Peripheral cytokines may cross the blood-brain barrier by diffusion (i.e., volume transmission) or active transport. In addition, peripheral cytokines may activate the vagus nerve, which in turn induces cells in the brain (e.g., microglia) to produce cytokines.

Question 27

stress-induced affective disorders with hippocampal damage and the effects of antidepressants

Answer 27

Chronic stress is theorized to produce depression through brain damage.
Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are critical regulators of the formation and plasticity of neuronal networks. Animal studies have shown that chronic stress reduces BDNF activity in the hippocampus which contributes to the atrophy of neurons, and that this reduction can be prevented by treatment with antidepressant drugs that may increase the dendritic arborizations and survival of the neurons, or help repair or protect the neurons from further damage. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD).

Figure from Nestler, Hyman & Malenka: Molecular Neuropharmacology, Fig. 15-7, p. 350.

Details:
Model of the neurotrophic hypothesis of antidepressant treatments and stress-related disorders. The major cell types in the hippocampus and the effects of stress and antidepressant treatments on CA3 pyramidal cells are shown. The three major subfields of the hippocampus – CA3 and CA1 pyramidal cells and dentate gyrus granule cells – are connected by the mossy fiber (mf) and Schaffer collateral (sc) pathways. Chronic stress decreases the expression of brain-deprived neurotrophic factor (BDNF) in the hippocampus, which in turn may contribute to the atrophy of CA3 neurons and their increased vulnerability to a variety of neuronal insults. Chronic elevation of glucocorticoid levels is also known to decrease the survival of these neurons. In contrast, antidepressant treatments increase the expression of BDNF, as well as that of TrkB, and prevent the down-regulation of BDNF elicited by stress. Such activity may increase the dendritic arborizations and survival of the neurons, or help repair or protect the neurons from further damage.

Question 28

experimental models of depression

Answer 28

Reserpine-induced reduction of motor activity
Depression of active responding induced by 5-hydroxytryptophan
Clonidine withdrawal
Tail suspension test
Neonatal clomipramine
Lesioning of the dorsomedial amygdala in dogs
Isolation/separation – induced depression in monkeys
Exhaustion stress
Uncontrolled shocks (“learned helplessness”)
Genetic selection
Swim test immobility
Chronic mild stress

Question 29

posolt forced swim test

Answer 29

behavioral despair
-, rats or mice are placed in a pool of water for a pre-set number of minutes, during which they are constantly monitored. The animals alternate between swimming and adopting a passive floating posture. Because rats and mice are natural swimmers, this passive floating posture is seen as a depression-like behavior: they have given up. A drug would be considered antidepressant by PST if the animal spends less time floating passively and more time swimming actively.

Question 30

chronic mild stress induced anhedonia

Answer 30

Webster’s definition: a psychological condition characterized by inability to experience pleasure in normally pleasurable acts.

Operational definition: a decrease in behavioral responses for rewarding stimulus.

Behavioral (Operational) Measures.
- Ingestion of a palatable liquid
- Instrumental responding for rewarding brain stimulation

Question 31

chronic mild stress protocol

Answer 31

involves submitting animals to a series of unpredictable mildly stressful aversive situations. For example, limited amounts of food deprivation or water deprivation, continuous lighting in the cage, cage tilt, grouped housing, soiled cage, empty water bottle, strobe light, and white noise. Then a preference test involving a choice of water and tasty solution is provided for comparison of intakes between control and stress-treated animals.

Question 32

chronic mild stress and sucrose intake

Answer 32

Here are the results of one such testing procedure. After four weeks of chronic mild stress, stressed animals drank significantly less 1% sucrose than controls. The procedure has made them relatively anhedonic.

Question 33

maprotiline

Answer 33

a tetracyclkic antidepressant (TeCA),

Question 34

bupropion

Answer 34

is a NE-DA reuptake inhibitor (NDRI).

Question 35

mitrazapine

Answer 35

is a NE and 5-HT acting drug (NaSSA) and can also be classified as a t (TeCA). It works by blocking the alpha 2-adrenergic auto- and heteroreceptors (enhancing serotonin release), and selectively antagonizing the 5-HT2 and 5-HT3 serotonin receptors in the central and peripheral nervous system. It also enhances serotonin neurotransmission at 5-HT1 receptors and blocks the histiminergic (H1) and muscarinic receptors.

Question 36

mechanism of action MAOI

Answer 36

• Inhibition of MAO
  - irreversible (new enzyme synthesis) Tranlcypromine
  - reversible Moclobemide
  
  • Require time (2-4 weeks) to begin effectiveness; therefore other mechanisms likely to be involved

Question 37

effects of MAOI

Answer 37

• Mood elevation
  
  • CNS stimulation (mild amphetamine-like effect)

Question 38

therapeutic uses of MAOI

Answer 38

• Moderate to severe depression
  
  • Treat hypersomnia
  • Phobias
  • Panic attacks

Question 39

pharmacokinetcs of MAOIs

Answer 39

• Well absorbed from GI tract
  
  • Enzyme regeneration requires weeks; therefore delay use of other antidepressant therapy
  • Excreted in urine

Question 40

adverse effects of MAOIs

Answer 40

• Hypertensive crises
• tyramine in beer, red wine, aged cheeses, chicken liver
• tyramine releases CAs
• suicide potential
• Drowsiness, blurred vision, xerostomia, urinary retention, constipation
• Orthostatic hypotension
• Weight gain
• notable because monoamine oxidase inhibitors prevent the breakdown of tyramine. Tyramine (TIE-ruh-meen) is an amino acid that helps regulate blood pressure. It occurs naturally in the body, and it’s found in certain foods. If you take an MAOI and you eat high-tyramine foods, tyramine can quickly reach dangerous levels and can cause a serious spike in blood pressure and require emergency treatment.

Question 41

irreversible inhibition

Answer 41

in which the inhibitor binds with the enzyme by a strong covalent bond (i.e., like at an allosteric receptor) and inhibits the enzyme activity. Hence, it is difficult to unbind the inhibitor from the enzyme. Therefore, it is not possible to reverse the reaction. New enzyme must be synthesized. Tranylcypromine is used to treat major depressive disorder, including atypical depression, especially when there is an anxiety component, typically as a second line treatment

Question 42

reversible inhibition

Answer 42

(like a competitive antagonist) the inhibitor inactivates the enzyme by binding non-covalently with it. Hence, the reversible inhibition is not a strong interaction between the enzyme and the inhibitor. Thus, by increasing the concentration of the substrate, this can be easily reversed, and it is possible to reactivate the enzyme easily.

Question 43

mechanism of action of tricyclic antidepressants (TCA)

Answer 43

*Inhibit neuronal reuptake in NE, 5-HT and DA neurons
*Require 2-4 weeks for effect to appear
*Therefore other mechanism(s) likely

Question 44

effects of TCA

Answer 44

*Elevate mood
*Improve mental alertness
*Increase physical activity
*Reduce morbid preoccupation

Question 45

therapeutic uses of TCA

Answer 45

*Severe endogenous depression (initial treatment usually 4-8 weeks)
*Some phobias
*Enuresis
*Some pain syndromes
*Prophylaxis of migraine
*Bulimia
*OCD

Question 46

pharmacokinetics of TCA

Answer 46

*Lipophilic
*Well absorbed from GI tract
*Widely distributed
*Long half-lives
*Large first-pass effect, therefore low and inconsistent bioavailability
*Metabolized by liver and excreted by kidneys

Question 47

adverse effects of TCAs

Answer 47

*Antimuscarinic (blurred vision, xerostomia, urinary retention, constipation; aggravates glaucoma)
*Cardiovascular – cardiac overstimulation (catecholamines); slow AV conduction in elderly
*Orthostatic hypotension
*Overdose potentials in depressed (1-week supply)
*Drug interactions

Question 48

changes in adrenergic receptors and in norepinephrine synthesis and release with chronic antidepressant treatment

Answer 48

Chronic treatment with tricyclic antidepressant (TCAs) produces several changes in the function of the target neurons of norepinephrine (NE) neurons as well as in the NE neuron itself. The net effect of these changes is summarized by the arrows.

Question 49

SSRIs

Answer 49

Drugs
*Fluoxetine
*Sertraline
Advantages
*Fewer anticholinergic and cardiovascular side effects
*However, long-term effects need to be evaluated

Question 50

desensitization of 5-HT autoreceptors with chronic antidepressant treatment

Answer 50

SSRIs seem not only to limit reuptake of serotonin, there’s also evidence of reducing activity of 5-HT autoreceptors. Note the increased number of presynaptic vesicles.

Question 51

ketamine

Answer 51

Successful in treating Treatment Resistant Patients (TRPs)
A short iv subanesthetic dose of ketamine reduces depression in 65 to 70 % of TDPs
Effects lasts for only about one week (with some exceptions)
Ketamine has a short half-life
Mechanism of action is unknown, but may act through neuroplasticity and increased BDNF
Rapidly increases synaptic function in medial prefrontal cortex
Esketamine is a nasal spray and chemically similar to ketamine
Esketamine was approved in March 2019 for use in treating depression

Question 52

ketamine sites of action

Answer 52

Basic research studies demonstrate that ketamine causes a rapid and transient burst of glutamate in the prefrontal cortex, in part via disinhibition of GABA-ergic neurons that exert negative control over glutamatergic firing. There are also other muscarinic, cholinergic targets with the potential to produce rapid-acting antidepressant effects.
Rapid-acting antidepressants, notably ketamine, cause a burst of glutamate that results in an increase in synaptogenesis that has been compared with long-term potentiation (LTP). The increase in glutamate is thought to occur via blockade of N-methyl-Daspartate (NMDA) receptors located on inhibitory γ-aminobutyric acid (GABA)–ergic neurons, resulting in disinhibition of glutamate transmission. T

Question 53

lithium

Answer 53

Effects
*Reduces mania and onset of manic episodes
Therapeutic Uses
*Acute mania (effects may be delayed 2-3 wks)
*Prevention of bipolar illness
*Supplement antidepressant treatments
Pharmacodynamics
*Readily absorbed from GI tract
*Passage through BBB - slow
*Does not bind to plasma proteins
*Renal excretion
*Secreted into milk
Mechanism of Action
*Unclear
*Inhibits hormone-sensitive adenylate cyclase
*Also alters IP3 and PAG
*Stabilizes DA- and -adrenergic receptors
*May decrease NE and DA turnover
Adverse Effects
*Low therapeutic index
*Anorexia, vomiting, nausea, diarrhea, thirst, polyuria, fatigue, confusion
*Birth defects
*Thyroid enlargement
*Marked drug interactions with drugs that alter Na+ excretion

Question 54

possible sites of action of lithium

Answer 54

In addition, lithium may inhibit excitatory neurotransmission at glutamate synapses and stimulate neurotransmission at GABA synapses to reduce neurotransmission overall.

Question 55

electroconvulsive therapy

Answer 55

1900’s observed that spontaneous seizures improved psychiatric state
Early seizures induced with camphor and oil
1938 ECT
ECT generally used on depressed patients unresponsive to pharmacotherapy
Its efficacy is 80% to 90% which is higher than conventional therapies
Technically difficult and expensive
Must be administered several times a week for several weeks
Mood changes are due to cortical seizures and not to peripheral results
Mechanisms are not knownUsed for both unipolar and bipolar depression
Low incidence of side effects
Differences in “dosing” based on age, gender and medication use.
In general, seizure threshold is lower for younger compared to older patients, and lower for women than for men.

Question 56

behavioral activation therapy

Answer 56

• Focuses on getting individuals to engage in behaviors that are part of a meaningful life, even when they don’t feel like it  “action precedes motivation”
  
  • Could be as simple as getting out of bed or as involved as joining a social club, based on current level of functioning
  • Often, individuals improve just by engaging in meaningful activities, building mastery and gaining positive experiences

Question 57

progression of changes in treatment of major depressive disorder

Answer 57

In the 1960s depression and its treatments were classified separately from anxiety plus anxiety disorder subtypes and their treatments.

In the 1970s and 1980s there began to be an overlap between the use of traditional antidepressants and traditional anxiolytics for treatment of some anxiety disorder subtypes and mixtures of depression and anxiety, but not for generalized anxiety disorder.

By the 1990s the serotonin selective reuptake inhibitors (SSRIs) replaced classical anxiolytics as first-line treatment for anxiety disorder subtypes and for mixtures of anxiety and depression but not for generalized anxiety disorder.
In the late 1990s the antidepressants venlafaxine XR and others have become first-line treatments for generalized anxiety disorder. Thus, antidepressants are now first-line treatments for both depression and anxiety disorders, rendering the classification of antidepressant versus anxiolytic inappropriate for many antidepressants.