Mental Health Part A - Depression, Anxiety & Sleep Disorders
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Mood disorder characterized by alterations in cognition, behavior, and physical functioning.
It is a constellation of symptoms that interfere with normal function and may render an individual unable to perform psychologically, emotionally, and cognitively at previously attainable levels.
Among the cardinal symptoms are depressed mood, sadness, hopelessness, sleep disturbance, changes in appetite and weight, loss of interest, guilt, difficulty concentrating, and suicidal ideation.

Physiologic
Social
Genetic
Environmental
Biochemical

Serotonin hypothesis: a functional or an absolute deficiency in the neurotransmitter serotonin.
Catecholamine hypothesis: a functional or an absolute deficiency in the neurotransmitters norepinephrine, serotonin, or dopamine.
Permissive hypothesis: diminished serotonin gives "permission" for a superimposed norepinephrine deficiency to manifest as depression.
Beta-adrenergic receptor hypothesis: depression results from increased beta-adrenergic receptor sensitivity.

Postpartum depression
Seasonal affective disorder
Major depression with melancholic features
Major depression with psychotic features

Nonpharmacologic Treatment
Pharmacologic Treatment
Goals of Drug Therapy
Optimal drug therapy not only resolves the acute symptoms of depression but also reduces the risk of relapse (American Psychiatric Association, 2010).

Acute treatment phase: 6 to 8 weeks, up to 12 weeks.
The goal is to treat the patient until full remission and a return to the premorbid level of function.
Continuation phase: the time after a treatment response is seen in the acute phase and usually lasts 9 months to 1 year.
The practitioner should continue antidepressant therapy for 4 to 6 months after symptom resolution.
Maintenance phase: long-term or indefinite therapy.

A practitioner is explaining to a patient how his antidepressant acts to alleviate his symptoms of depression. Antidepressants act by:
A. Increasing monoamine oxidase (MAO) enzymes
B. Inhibiting the reuptake of the neurotransmitter
C. Turning off associated receptors
D. Decreasing norepinephrine in the system

B. Inhibiting the reuptake of the neurotransmitter
Rationale: Antidepressant agents can (1) block the MAO enzymes-MAO inhibitors, (2) inhibit the reuptake of the neurotransmitter, or (3) agonize or antagonize an associated receptor. In effect, each mechanism increases the available concentration of the neurotransmitter.

There are four common strategies used to modify drug therapy in the depressed patient: dosage increase/optimization, switching to a different drug within the same class or switching to a drug in a different class, augmenting the current drug, or combining medications.
Increasing the dose of a drug is typically recommended if the patient has had a response or a partial response during the first few weeks.
If an inadequate response or lack of response occurs within the first few weeks of therapy, a switch to a different drug may be warranted.

Selective serotonin reuptake inhibitors
Serotonin norepinephrine reuptake inhibitors
Tricyclic antidepressants
Monoamine oxidase inhibitors
Atypical antidepressants
Bupropion
Trazodone
Nefazodone
Mirtazapine
Novel drugs

A practitioner is prescribing Cymbalta for a patient with depression. What class of drugs is this agent?
A. Tricyclic antidepressants
B. Selective serotonin reuptake inhibitors
C. Serotonin-norepinephrine reuptake inhibitors
D. Atypicals

C. Serotonin-norepinephrine reuptake inhibitors
Rationale: Cymbalta, which is dosed at 40-60 mg to start with, is an serotonin norepinephrine reuptake inhibitors (SNRI).

First line: selective serotonin reuptake inhibitors (SSRIs) and SNRIs
Second line: atypical antidepressant
Third line: tricyclic antidepressants (TCAs) and monoamine oxidase inhibitor

Children and adolescents
Geriatrics
Pregnancy
Emergencies

A practitioner is prescribing first-line therapy for a patient with depression. What is the agent of choice?
A. Atypical antidepressant
B. TCA
C. Novel drug
D. SSRI

D. SSRI
Rationale: First-line therapy for a patient with depression is an SSRI. Second line is an atypical antidepressant, and third line is MAOs or TCA depending on past response to other agents and side effect profile.

Depression is the leading cause of suicide, and up to 80% of depressed patients experience suicidal impulses.
Since 1990, whether antidepressant drugs are linked to suicide has been an acrimonious debate.
Some argue that depressed adolescents who are suicidal and treated with antidepressants may regain initiative and energy before improvement in cognition and mood, thereby becoming mobilized to attempt suicide.
Others argue that the medication prescribed to treat depression is responsible for causing adolescents to attempt suicide.

Panic disorder
Agoraphobia
Separation anxiety
Selective mutism
Specific phobia
Social anxiety disorder
Generalized anxiety disorder

Anxiety disorder due to a general medical condition
Substance-/medication-induced anxiety disorder
Anxiety disorder not otherwise specified

Physiological factors
Genetic factors

Neurobiologic factors
Norepinephrine, serotonin, and gamma-aminobutyric acid (GABA) are the major neurotransmitters studied in relation to the pharmacologic treatment of anxiety. People with anxiety disorders, especially panic disorder, are found to have malfunctioning noradrenergic systems with a low threshold for arousal.

Anxiety disorders most commonly begin in early adulthood, tend to be chronic with waxing and waning periods of remission and relapse, and frequently continue into old age.
In children, anxiety may develop, particularly in relation to school, and late onset of an anxiety disorder is rare but can occur.
In older adults, anxiety disorders are the most common psychiatric disorders seen.

A multitude of special challenges exists with respect to the diagnosis and successful treatment of generalized anxiety disorder (GAD).
As previously discussed, many patients present with physical complaints and no recognition whatsoever of an emotional or a psychiatric component.
Patients may lack an understanding of mental illness, may deny symptoms or its existence when given the diagnosis of a mental illness, or be so ashamed of the stigma associated with mental illness that they are prevented from being open to discussing treatment options.

Which of the following is a neurobiologic factor related to the causes of anxiety disorders?
A. Somatic complaints
B. Medical illnesses
C. Neurotransmitters
D. Family history of anxiety disorder

C. Neurotransmitters
Rationale: The modulation of normal and pathologic anxiety states is associated with multiple regions of the brain and dysregulation in several neurotransmitter systems (norepinephrine [NE], serotonin [5-HT], GABA, corticotrophin-releasing factor [CRF], and cholecystokinin). Somatic complaints and medical illnesses are physiologic causes, and family history of anxiety is a genetic cause of anxiety.

Psychoeducation
Supportive counseling
Behavioral therapy
Cognitive therapy
Stress management techniques
Meditation
Exercise

Remission.
Complete resolution of anxious symptoms.
Return to premorbid functionality and quality of life.
The ideal anxiolytic medication should promote calmness without resulting in daytime sedation and drowsiness and without producing physical or psychological dependence.

Antidepressants
Selective serotonin reuptake inhibitors
Serotonin-norepinephrine reuptake inhibitors
Tricyclic antidepressants
Benzodiazepines (BZDs)
Treatment of BZDs overdose (important to know) - flumazenil (Romazicon).

Azapirones
Novel drugs
Monoamine oxidase inhibitors
Other antianxiety medications
Atypical antipsychotics

A practitioner is prescribing Celexa for a patient with GAD. What category of drug is Celexa?
A. Tricyclic antidepressants
B. Selective serotonin reuptake inhibitors
C. Serotonin-norepinephrine reuptake inhibitors
D. Monoamine oxidase inhibitors

B. Selective serotonin reuptake inhibitors
Rationale: Considered one of the two first-line pharmacotherapeutic options for the management of GAD in the United States, the selective serotonin reuptake inhibitors (SSRIs) such as Celexa are thought to improve anxious symptoms by inhibiting the reuptake of serotonin in the synaptic cleft.

First line: SSRI or serotonin-norepinephrine reuptake inhibitors (SNRI); useful for anxiety disorder as well as a coexisting comorbidity.
Second line: buspirone.
Third line: consists of a tricyclic antidepressants alone or buspirone.
Fourth line: After the SSRIs, SNRIs, buspirone, and imipramine are exhausted; combination or adjunctive therapy may be considered.

A practitioner is considering second-line therapy for a patient who is diagnosed with GAD. What is the recommended treatment option?
A. Cognitive-behavioral therapy (CBT)
B. SSRIs
C. SNRIs
D. Buspirone

D. Buspirone
Rationale: After confirmed failure or intolerance to multiple members of the SSRI and SNRI classes at appropriate doses for an appropriate period of time, imipramine or buspirone may be considered. Buspirone may be more appropriate if sedation or psychomotor impairment would be dangerous.

First-line therapy
Nonpharmacologic therapy, such as CBT
SSRIs or venlafaxine
Second-line therapy
A different SSRI or venlafaxine
Third-line therapy
Yet another SSRI, imipramine, or an monoamine oxidase (MAO) inhibitor

First-line therapy
SSRIs and venlafaxine and CBT
Second-line therapy
MAO-I phenelzine for selected patients.
Due to adverse effect profile, toxicity in overdose, and drug- and food-interaction potential, phenelzine should be reserved for refractory cases.

Pediatric
Geriatric
Pregnancy

Drug information: The patient should know the name of the drug prescribed, dose, frequency of administration, expected outcome of therapy, drug interactions, adverse events, and the amount of time it will take for the drug to take effect.
Lifestyle information: The patient should know that the physical symptoms of anxiety (e.g., increased heart rate, palpitations, pupillary dilatation, trembling, increased perspiration, muscle tension, and sleep disturbances) are not life threatening.

With 10 different types, the anxiety disorders represent the largest group of psychiatric disorders.
Between 35% and 50% of individuals with major depression meet criteria for GAD.
Anxiety disorders usually begin in early adulthood, tend to be chronic, with interspersed periods of remissions and relapses, and they frequently continue into old age.
Left untreated, the patient's sphere of comfort may continue to constrict until daily activities become limited and normal function is impaired.

Definition
Persistent trouble sleeping
Causes
Medical
Psychiatric
Drug and alcohol abuse
Primary sleep disorders

The prevalence of chronic insomnia in the general population is between 10% and 35% and affects more women than men.
Characteristics of chronic insomnia include somatized tension and acquired habits that prevent either the initiation or maintenance of sleep. Life stresses such as shift work, a family tragedy, or physical pain can exacerbate chronic insomnia.

Short-term insomnia can be in isolation or comorbid with mental disorders, medical conditions, or substance abuse.
Many features of short-term insomnia are shared with chronic insomnia with the primary difference of duration. Circadian rhythm disorders, jet lag, and rotating shift work should be considered in the differential.

Stage I: Light NREM: dreamlike state, lasts a few minutes
Stage II: Relatively light NREM: fragmented thoughts, lasts 15 to 20 minutes
Stage III-IV: Deep NREM: lowering of blood pressure, cerebral glucose metabolism, heart rate, and respiratory rate, starts 35 to 40 minutes after falling asleep and lasts 40 to 70 minutes

REM sleep: Starts after 90 minutes of sleep, lengthens toward the end of the night; this cycle alternates throughout the night at intervals of 90 to 100 minutes, four to six times per night

In which stage of sleep does, a person experience lowering of blood pressure, cerebral glucose metabolism, heart rate, and respiratory rate?
A. Stage I
B. Stage II
C. Stage III-IV
D. REM sleep

C. Stage III-IV
Rationale: In stage III-IV, deep NREM occurs with lowering of blood pressure, cerebral glucose metabolism, heart rate, and respiratory rate; it starts 35 to 40 minutes after falling asleep and lasts 40 to 70 minutes. In stage I, light NREM occurs with a dreamlike state that lasts a few minutes. In stage II, relatively light NREM occurs with fragmented thoughts for 15 to 20 minutes. REM sleep starts after 90 minutes of sleep and lengthens toward the end of the night.

What kind of work does the patient do? Is there shift work involved, and which shift?
What time does the patient go to bed?
What kind of bed partner does the patient have, if any?
Does the patient take prescription or OTC drugs?
How many times a night does the patient awaken?
What does the patient do if they cannot go to sleep?
Does the patient take daytime naps?

Symptom pattern
Treatment goals
Past treatment responses
Patient preference
Cost
Medication interactions
Side effects

Benzodiazepines
When choosing a benzodiazepine, the practitioner should select an agent with an onset of action that matches the patient's complaint.
Choose an agent with a short duration of effect, lacks rebound insomnia, and causes few or no cognitive problems (e.g., hangover, lack of motor coordination, or memory disturbance).

Benzodiazepine receptor agonist
This class of hypnotics was developed to improve the safety profile of the barbiturate-type and longer-acting benzodiazepine compounds.
Benzodiazepine receptor agonists (BRZA) pharmacologically are like benzodiazepines but instead mimic GABA action, an inhibitory transmitter, which induces sleepiness.

Orexin receptor antagonists are a new class in the treatment of insomnia. There are two agents in the class, suvorexant (Belsomra) and Lemborexant (Dayvigo)
There are two approved melatonin receptor agonists for use in the United States but for different sleep indications. Ramelteon (Rozerem) was introduced in 2005 as an option to treat insomnia. The other is tasimelteon (Hetlioz) that is only approved for the treatment of circadian rhythm disorder or to shift the sleep-wake cycles of those who are blind.
Antihistamines are one of the most used classes of OTC sleep-inducing agents. These drugs often come in combination with analgesics such as acetaminophen and ibuprofen.

A practitioner is prescribing Ambien CR for a female patient who is diagnosed with insomnia. What is the recommended dosage for this client?
A. 6.25 mg PO QHS
B. 1-2 mg PO QHS
C. 0.125 mg PO QHS
D. 15 mg PO QHS

A. 6.25 mg PO QHS
Rationale: The starting dosage for Ambien CR is Female: 6.25 mg PO QHS; max 12.5 mg and Male: 6.25-12.5 mg PO QHS.

First line: benzodiazepine (e.g., alprazolam, lorazepam, temazepam), BZRAs (zolpidem, zaleplon) or ramelteon; first-generation antihistamine-doxylamine succinate
Second line: alternating short-acting BZRAs (zaleplon, eszopiclone) with ramelteon; sedating antidepressants (trazodone, amitriptyline, doxepin, mirtazapine)
Third line: sedating antiepilepsy agents (gabapentin) or atypical antipsychotics (quetiapine, olanzapine); orexin receptor antagonist (suvorexant)

A practitioner is starting therapy for a patient newly diagnosed with insomnia. What would be a recommended agent to begin treatment for this patient?
A. Alternating short-acting BZRAs with ramelteon
B. Sedating antidepressants
C. Benzodiazepine
D. Atypical antipsychotic

C. Benzodiazepine
Rationale: First-line therapy for insomnia is a benzodiazepine and first-generation antihistamine-doxylamine succinate. Alternating short-acting BZRAs (zaleplon, eszopiclone) with ramelteon and sedating antidepressants (trazodone, amitriptyline, doxepin, mirtazapine) are second-line treatments. Sedating antiepilepsy agents and antipsychotics are third-line treatments.

Pediatric: Use of barbiturates in the pediatric population is usually limited to those who have seizure disorders. In general, benzodiazepines are not indicated for children younger than age 15.
Geriatric: It is important to evaluate the geriatric patient for underlying comorbidities that contribute to insomnia.
Women: Pharmacokinetic differences have been noted when select BZRA agents are prescribed for women.

Patient-oriented information sources
Nutrition/lifestyle changes
Complementary and alternative medication

A compelling urge to move limbs associated with paresthesias/dysesthesias
Motor restlessness as evidenced by the following:
Floor pacing; tossing and turning in bed; rubbing legs
Symptoms worse or exclusively present at rest with variable and temporary relief by activity
Symptoms worse in the evening and at night

Nocturnal leg cramps
Akathisia
Peripheral neuropathy

Age of patient
Severity of symptoms
Frequency/regularity of symptoms
Presence of pregnancy
Renal failure

Narcolepsy is a sleep disorder caused by deficits in the hypocretin signaling in the brain, leading to poor sleep-wake cycles that can greatly impact those affected daily activities. Individuals with narcolepsy sleep the same amount as the average person but cannot control their sleep timing.
Patient presentations include complaints of excessive daytime sleepiness (EDS), cataplexy, and sleep-related hallucinations, along with sleep paralysis. These criteria are commonly known as the narcoleptic triad.

Psychostimulants (Wake-Promoting Agents)
Amphetamines
Sodium Oxybate
Antidepressants
Histamine H3 Antagonist/Inverse Agonist
Dopamine-norepinephrine reuptake inhibitors

Sleep disorders can affect the quality of sleep and therefore how individuals function on a daily basis. Poor sleep can often be a symptom of other underlying physical or psychiatric problems.
Sleep disorders include insomnia, snoring and sleep apnea, narcolepsy, and chronic sleep deprivation.
Pharmacologic therapy is not appropriate for snoring and sleep apnea but has a role in the management of the other diagnoses.