2© Paradigm Publishing, Inc. Chapter 8 Drug for Psychiatric and Mood Disorders.

© Paradigm Publishing, Inc. 2

Chapter 8

Drug for Psychiatric and Mood Disorders


Chapter 8

Topics

• Anatomy and Physiology of Neurotransmission• Depression• Anxiety• Insomnia• Bipolar Disorder• Schizophrenia and Psychosis• Herbal and Alternative Therapies


Anatomy and Physiology of Neurotransmission

Neurotransmitters • Are chemicals that transmit signals from nerve cell to

nerve cell within the brain• Includes serotonin, norepinephrine, and dopamine• Are released from a cell, cross the synaptic cleft, connect

with receptors on membranes of adjacent cells Are then either taken back up into presynaptic nerve

cell (a process called reuptake) or broken down by metabolic enzymes while in the cleft



Neurotransmitters (continued)• Monoamine oxidase

Is an enzyme that breaks down neurotransmitters in neurons

• Disorders affecting mood and mental function are related to deficiency or dysfunction of neurotransmitters

• Drug therapy manipulates levels of neurotransmitters Mimics their actions or alters the processes that

eliminate them from the synaptic cleft Allows them to remain in the synaptic cleft longer and

activate more receptors



Signal Conduction Across the Synaptic CleftDrug therapy either blocks reuptake or breakdown of neurotransmitters


Depression

About Depression• Treatment accounts for several of the top 50 prescription

medications in the United States• Two types

Exogenous (external) sources, such as the response to the death of a loved one

Endogenous (internal) causes that do not have logical, observable reasons for happening

Is more likely to require drug therapy to control• Neurotransmitters involved in mood include

norepinephrine, serotonin, and dopamine


Depression

Signs Crying (often no cause), no interest in life or social activities, increased focus on death, and significant weight loss or gain

Symptoms Low self-esteem, pessimism, difficulty sleeping, loss of energy and ability to think, confusion, poor memory, feeling worthless and guilty, and thoughts of suicide


Depression

Antidepressants • Includes SSRIs, SNRIs, TCAs, MAOIs, bupropion, and

trazodone• Takes 3–6 weeks for patients to feel effects

Takes time for the number of receptors for transmitters to increase and cells to adapt

• Drug therapy trial should last 3–4 weeks• Doses should only be changed once a month by prescriber• Caution: do not stop use abruptly because it may worsen

symptoms Gradually decrease doses


Depression

Antidepressants: SSRIs and SNRIs• Indications: first-line therapy for depression• Indications (other) for SSRIs: OCD, PMDD, anxiety, and panic

disorders OCD

Is a form of anxiety where obsessive thoughts intrude daily life and impair function

PMDDIs emotional and behavioral changes in the second

half of menstrual cycle; more severe than PMS• Indication for Duloxetine (primary): nerve pain that

accompanies depression


Depression

Antidepressants: SSRIs and SNRIs (continued)• Mechanism of Action

SSRIs block serotonin reuptake into presynaptic neuron SNRIs block reuptake of serotonin and norepinephrine

• Side Effects (frequent): sexual dysfunction causes many patients to stop therapy

• Side Effects of SSRIs: nausea, vomiting, dry mouth, drowsiness, insomnia, headache, and diarrhea

• Side Effect of Fluvoxamine: can cause weight loss; sometimes used for eating disorders including bulimia

• Routes: all are oral


Depression

Antidepressants: SSRIs and SNRIs Cautions• Possible increased risk of suicide in early weeks of therapy,

especially in pediatric and adolescent patients Patients require close monitoring and should be offered

counseling and psychotherapy• Increase risk for serotonin syndrome; potentially fatal

Occurs if too much serotonin is present Can cause changes in cardiovascular function and heart

attacks Risk very high if patient is taking more than one

antidepressant or St. John’s wort (herb product)


Depression

Antidepressants: TCAs• Name comes from three-ring structure• Mechanism of Action: block reuptake of norepinephrine

and/or serotonin• Indications: depression, insomnia, and nerve conditions• Tetracyclic agent is a TCA but has a four-ring structure• Side Effects: drowsiness, anticholinergic effects (dry

mouth, blurred vision, constipation, and urinary retention) Some also cause priapism (erection more than 4 hours)

• Routes: All are oral; amitriptyline is also IM


Depression

Antidepressants: TCAs Cautions• Causes cardiotoxicity and heart arrhythmias; do not take if

preexisting heart conditions or recent heart attack• Causes postural hypotension• Do not take if have seizure disorders (for most patients)• Do not take if liver problems; can cause liver toxicity• Do not take with MAOIs due to serotonin syndrome risk

Washout required if switching from TCA to MAOI• Overdose can be fatal


Depression

Antidepressants: MAOIs• Indication: last resort for intractable depression symptoms• Mechanism of Action: inhibit a primary enzyme that

metabolizes neurotransmitters, so levels rise in cleft• Side Effects: heart palpitations, postural hypotension,

dizziness, headache, tremors, insomnia, anxiety, restlessness, agitation, and anticholinergic effects

• Cautions: interact with many drugs; interact with tyramine-rich foods such as aged cheeses, beer, wine, sauerkraut, and pickled foods


Depression

Antidepressants: Bupropion• Mechanism of Action: mainly blocks dopamine reuptake;

also weakly blocks serotonin and norepinephrine reuptake • Indication: depression symptoms, adjunct therapy for

smoking cessation, and anxiety• Side Effects: headache, agitation, weight gain, insomnia• Cautions

Do not chew or crush extended-release form Do not take if have seizure disorders Do not take with alcohol or CNS depression drugs

• Route: all are oral


Depression

Antidepressants: Trazodone• Mechanism of Action: not fully understood, but it may

affect serotonin reuptake• Indication: depression with insomnia, neuralgic pain, and

anxiety that affects sleep• Side Effect: drowsiness• Route: oral


Anxiety

About Anxiety• Is the abnormal function of the neurotransmitters that

regulate brain activity, mood, and the fear response• Two types

Panic disorderCauses chest pain, difficulty breathing, palpitations,

dizziness, sweating, choking sensation, trembling, and unrealistic feelings of doom

Symptoms occur without typical stimuli; onset of symptoms is sudden and quick; called an attack


Anxiety

About Anxiety (continued)• Two types (continued)

Generalized anxiety disorderIs excessive worry that causes significant distress or

disturbs normal functioningCauses restlessness, irritability, difficulty concentrating,

muscle tension, and fatigueSymptoms are constant, can become debilitating

• PTSD Is a variation of anxiety Occurs in response to a traumatic event and reexperiencing

syndrome continues for at least a month Symptoms include avoidance behavior and irritability


Anxiety

Sedatives and Hypnotics • Anxiety often requires drug therapy and counseling• Hypnotics

Are medications that causes sedation and relaxation• Sedatives (another word for hypnotics)

Used to induce sleep• Agents with sedatives or hypnotics like benzodiazepines

may be useful for short-term treatment for panic disorder Benzodiazepines typically are necessary for generalized

anxiety disorder• SSRIs are also used for PTSD and anxiety


Anxiety

Sedatives and Hypnotics: Benzodiazepines • Indications: first-line drug for generalized anxiety disorder,

panic disorder, and PTSD• Indications (other): preanesthetic medications, alcohol

withdrawal symptoms, and status epilepticus• Mechanism of Action: stimulate omega receptors in the

CNS, causing drowsiness and relaxation Used for anxiety and has calming and euphoria effect Used for sleep to improve sleep quality

• Routes: all are oral; a few are IM and IV


Anxiety

Sedatives and Hypnotics: Benzodiazepines (continued)• Side Effects (common): constipation, muscle weakness,

and impaired reflexes• Side Effects (other): difficulty waking up in the morning

and leftover drowsiness the following day• Side Effects (severe): oversedation and respiratory

depression• Cautions: do not take with alcohol or other sedatives; can

increase heart rate; all are controlled substances Schedule IV and require special handling and storage


Anxiety

Sedatives and Hypnotics: Buspirone• Mechanism of Action: blocks serotonin receptors• Indication: preferred antianxiety medication because is not

a controlled substance and doesn’t cause euphoria• Route: oral; must be taken regularly• Side Effects: drowsiness, dizziness, headache, and nausea• Side Effects (severe): hostility, depression, serotonin

syndrome, and extrapyramidal symptoms• Cautions: may cause depression and increase suicidal

tendencies; do not take with MAOIs

© Paradigm Publishing, Inc.

Your Turn

Question 1: A physician is writing an order for a patient who has depression. The patient also has nerve pain. What is the likely order?

Answer: The order is probably for duloxetine, an antidepressant that also is used for nerve pain that accompanies depression.

Question 2: A patient is experiencing reoccurring, sudden attacks in which she feels chest pain and has trembling, sweating, and difficulty breathing. She also feels something horrible is about to happen. What therapy will likely be prescribed?

Answer: Benzodiazepines are the first-line therapy for panic attacks.

24


Insomnia

About Insomnia• Is the inability to fall asleep (sleep latency) or

stay asleep (sleep maintenance) Is usually a reaction to a stressful situation and a

disruption in the normal sleep cycle• Can be symptom of depression, anxiety, or other mental

disorders

Drugs for Insomnia• First identify and eliminate external or medical

causes and implement good sleep hygiene Drug therapy is last resort and used short term


Insomnia

Drugs for Insomnia (continued)• Drug therapy

Begins with OTC antihistamines; short-term use Diphenhydramine, hydroxyzine, and TCAs

Can cause drowsiness as a side effect• Sleep aids

RamelteonNot a controlled substanceMechanism of Action: Mimics melatonin, a hormone of

the body’s natural sleep/wake cycleCautions: do not take with or immediately after high-

fat meals; many drug interactions


Insomnia

Drugs for Insomnia (continued)• Sleep aids (continued)

Eszopiclone, zaleplon, and zolpidem used short-term only (2 weeks or less)Side Effects (common): headache, drowsiness, dry

mouth, dizziness, nausea, hallucination, and memory loss

Side Effects (severe): face and tongue swelling, difficulty breathing, and sleepwalking (rare)

Cautions : controlled substances Schedule IV; require special handling and storage


Bipolar Disorder

About Bipolar Disorder• Is related to the dysfunction of neurotransmitters such as

GABA, serotonin, and norepinephrine• Is characterized by periods of depression with times of

mania Mania manifests as irritability, elevated mood,

excessive involvement in work or activities, grandiose ideas, racing thoughts, a decreased need for sleep

• Varies in how much a patients experiences mania versus depression

• Other psychoses often coexist with bipolar disorder


Bipolar Disorder

Drugs for Bipolar Disorder: Lithium• Is the first-line and primary drug therapy

Anticonvulsants and several atypical antipsychotic agents may be used instead of lithium

• Route: oral; dosed at 900–2,400 mg a day• Is a mood stabilizer that accompanies antidepressants• Side Effects (common): nausea, vomiting, dizziness,

tremors, fatigue, muscle weakness, increased thirst and urination, and significant weight gain

• Side Effects (severe): hypothyroidism, heart arrhythmias, and leukocytosis (an increase in white blood cells)


Schizophrenia and Psychosis

About Schizophrenia and Psychosis• Schizophrenia

Is related to an imbalance of various neurotransmitters, likely dopamine and serotonin

Comprised of positive symptoms (hallucinations and delusions) and negative symptoms (withdrawal, ambivalence, behavior changes, memory loss, and confusion)

Onset usually during teen or young adult years Drug therapy often needed to maintain normal

thought and function



About Schizophrenia and Psychosis (continued)• Schizophrenia is one of a variety of psychotic disorders

Reactive Psychosis

Occurs briefly, from a few hours to just under a month, and then subsides

Delusional Disorder

Delusional thoughts longer than 1 month; do not impair normal function

Schizophreniform Disorder

Symptoms similar to schizophrenia but less than 6 months; if symptoms continue for more than 6 months then a diagnosis of schizophrenia is made



About Schizophrenia and Psychosis (continued)• Psychotic symptoms

Patients with bipolar disorder can have thought disorders, hallucinations, or delusions

Half of patients with bipolar disorder will have at least one psychotic symptom at least once in their lifetime

Displayed in patients with dementia Can be caused by drugs



Drugs for Schizophrenia and Psychosis• Drug therapy highly individualized and often requires

changing therapies over time • Doses slowly increased over weeks to months, and then

adjusted to balance symptoms and side effects• Atypical agents

First-line therapy• Antipsychotics

Second-line therapy; have been available longer than atypical agents

Side effect profiles are problematic and often dose-limiting



Drugs: Typical Antipsychotics• Mechanisms of Action: not fully understood

Many drugs are phenothiazines or thioxanthenes, which block dopamine receptors that control emotion and thought

• Indications: reduces abnormal thoughts and hallucinations Does not always affect behaviors such as withdrawal

and ambivalence Haloperidol also for Tourette’s syndrome Prochlorperazine (low doses) also for nausea and

vomiting



Drugs: Typical Antipsychotics (continued)• Indications (other): used for agitation and delirium in

patients without schizophrenia Lower doses prescribed Given to elderly patients in long-term care that have

dementia and related effects like irritability, confusion, and delirium

Can cause dizziness, blood pressure drop, and fallsLaws and regulations in place for use of

antipsychotic agents in long-term care settings



Drugs: Typical Antipsychotics (continued)• Side Effects (common): sedation, dizziness, constipation,

dry mouth, blurred vision, weight gain, photosensitivity, and sexual function changes

• Side Effects (severe): EPS (tremors, muscular rigidity, and difficulty initiating movement) and tardive dyskinesia (uncontrollable tongue thrusting and lip smacking) Anticholinergics given to reduce EPS effects

• Routes: all are oral; some are also IM and IV• Cautions: can cause arrhythmias and heart function

changes; do not drink alcohol



Drugs: Atypical Antipsychotics• Mechanisms of Action: not fully understood

Some block dopamine and others enhance it• Indications: first-line therapy for schizophrenia and other

psychoses• Dosage: variable effectiveness for individual patients• Side Effects (common): drowsiness, headache,

constipation, dry mouth, urinary incontinence or retention, rash, excitation, hiccups, EPS (but less than typical antipsychotics), and a decrease in blood pressure



Drugs: Atypical Antipsychotics (continued)• Side Effects (severe): arrhythmias, QT wave prolongation,

and significant weight gain, which often causes high cholesterol levels and new-onset diabetes Medication for Type II diabetes will be needed

• Cautions: can lower seizure threshold; do not take if have liver or kidney problems; bone marrow suppression; use caution with elderly patients; do not drink alcohol

• Routes: all are oral; some are IM


Your Turn

Question 1: A patient is having difficulty staying asleep at night. He has tried OTC medications and follows good sleep hygiene. He wants a nonaddictive sleep aid. What medication is the prescriber likely to order?

Answer: The prescriber will likely order Ramelteon. This sleep aid is not a controlled substance and does not cause addiction.

Question 2: What is a restriction of typical antipsychotics?Answer: Patients cannot consume alcohol while taking these medications.


Herbal and Alternative Therapies

• Melatonin Is taken for sleep and insomnia disorders, benzodiazepine

and nicotine withdrawal, and headaches• Kava

Is taken for anxiety and insomnia Is effective but dangerous

• St. John’s wort Is taken for mild depression and psychological symptoms

of menopause• SAMe

Is taken for mild depression and osteoarthritis


Summary• SSRIs, TCAs, and MAOIs are used to treat depression• Benzodiazepines are the first-line therapy for anxiety• Benzodiazepines are also used for insomnia; typically

nonpharmacologic and OTC remedies are tried first• Ramelteon is a new prescription agent for insomnia;

enhances melatonin• Lithium is the drug of choice for bipolar disorder• Typical and atypical antipsychotics are used for

schizophrenia and psychosis; have significant side effects

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2© Paradigm Publishing, Inc. Chapter 8 Drug for Psychiatric and Mood Disorders.

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