Drugs for Treating Psychiatric Disorders

Chapter 13

What are Psychotropic Medications?

Medications are used to treat the symptoms of mental disorders such as schizophrenia, depression, bipolar disorder (sometimes called manic-depressive illness), anxiety disorders, and attention deficit-hyperactivity disorder (ADHD).

Side Effects to Psychotropic Drugs?

Some people get side effects from medications and other people don't

Factors that can affect how medications work in people include: Type of mental disorder, such as depression, anxiety, bipolar

disorder, and schizophrenia Age, sex, and body size Physical illnesses Habits like smoking and drinking Liver and kidney function Genetics Other medications and herbal/vitamin supplements Diet Whether medications are taken as prescribed.

DepressionSymptomsMost symptoms, felt most days over 2 weeks• Depressed mood most of the day, • Markedly diminished interest or pleasure • Significant weight loss when not dieting or weight

gain • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue or loss of energy • Feelings of worthlessness or guilt• Diminished ability to think or concentrate, or

indecisiveness• Recurrent thoughts of death

DepressionMost common drugs used:• Tricyclic antidepressants (TCAs) used mostly in the past

though no other group of antidepressants was been demonstrated as more effective or fast working)– Elavil, Tofranil, Pamelor

• Selective serotonin reuptake inhibitors (SSRIs)– Celexa, Prozac, Lexapro, Paxil, Zoloft

• Serotonin–norepinephrine reuptake inhibitors (SNRIs)– Effexor, Pristiq, Cymbalta, Dalcipran, Meridia

• Monoamine oxidase inhibitors MAOIs (used rarely)– Apresoline, Harmalol, Selegiline, Moclobemide

TCAs

• Orally (once a day at bedtime to minimize unwanted side effects like persistent sedation)

• 4 days of clinical effect and readily crosses the placental barrier

• Rapidly and almost completely metabolized by enzymes located in the liver.

• Urine

PharmacokineticsPharmacokineticsAbsorptionAbsorption

DistributionDistribution

MetabolismMetabolism

EliminationElimination

TCAsRelated NeurotransmittersRelated NeurotransmittersTherapeutic effects comes from blocking reuptake of dopamine, serotonin, and norepinephrineBlockade of ACH receptors results in dry mouth, confusion, memory impairments, and blurred visionBlockage of histamine receptors results in drowsiness and sedation

TCAsEffectsEffectsElevated mood

Increased physical activity

Improved appetite

Improved sleep patterns

Reduced morbid preoccupation

Clinically effective in the long-term therapy of dysthymia

Dry mouth

Confusion

Memory impairments

Blurred vision

Sedation*

Cardiac depression

Cardiac arrhythmias

SSRIsRelated NeurotransmittersRelated NeurotransmittersBlocks the re-uptake of serotonin

*Each drug has a different half life

SSRIsEffectsEffectsElevated mood

Increased physical activity

Improved appetite

Improved sleep patterns

Reduced morbid preoccupation

Clinically effective in the long-term therapy of dysthymia

Sexual dysfunction > 60%

Anxiety

Agitation

Insomnia

Rarely suicide

SSRIsCaution!Caution!Suicide

Serotonin syndrome (most likely to occur when SSRIs are combined with each other, other antidepressants, or valerian root)

- Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening.

Serotonin Withdrawal Syndrome (occurs in perhaps 60% of SSRI-treated patients following drug removal)

- Disequilibrium, gastrointestinal symptoms, sensory disturbances (sensation of electric shocks), sleep disturbances

SNRIsRelated NeurotransmittersRelated NeurotransmittersBlocks the reuptake of serotoninBlocks the reuptake of norepinephrine

SNRIsEffectsEffectsElevated mood

Increased physical activity

Improved appetite

Improved sleep patterns

Reduced morbid preoccupation

Clinically effective in the long-term therapy of dysthymia

Dry mouth

Dizziness

nausea

Blurred vision

Sedation*

SNRIsCaution!Caution!Suicide

Serotonin syndrome (most likely to occur when SSRIs are combined with each other, other antidepressants, or valerian root)

- Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening.

Serotonin Withdrawal Syndrome (occurs in perhaps 60% of SSRI-treated patients following drug removal)

- Disequilibrium, gastrointestinal symptoms, sensory disturbances (sensation of electric shocks), sleep disturbances

MAOIsRelated NeurotransmittersRelated NeurotransmittersBreaks down norepinephrine and serotonin permanently –which means it could be weeks before new neurotransmitters are manufactured.

MAOIsEffectsEffectsElevated mood

Increased physical activity

Improved appetite

Improved sleep patterns

Reduced morbid preoccupation

Clinically effective in the long-term therapy of dysthymia

Potential fatal blood pressure increases when mixed with common foods

MAOIsCaution!Caution!Death when mixed with common foods like cheese, wine, beer, soy, coffee, chocolate

Serotonin syndrome (most likely to occur when MAOIs are combined with each other, other antidepressants, or valerian root)

- Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening.

works on the neurotransmitter dopamine, is unique in that it does not fit into any specific drug type.

Wellbutrin (Bupropion)

Herbal Remedies for Depression?

NIH conducted a clinical trial to determine the effectiveness of treating adults who have major depression with St. Johns wort. The single-blind study included

340 people diagnosed with major depression.

1/3 took the herbal medicine, 1/3 took an SSRI, and 1/3 took placebo.

The study found that St. John's wort was no more effective than the placebo in treating major depression

Bipolar Disorder

Depressive Symptoms5 or more, in same 2 week period• Depressed mood most of the day, • Markedly diminished interest of pleasure • Significant weight loss when not dieting or weight

gain • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue or loss of energy • Feelings of worthlessness or guilt• Diminished ability to think or concentrate, or

indecisiveness• Recurrent thoughts of death

Bipolar Disorder

Mania Symptoms3 or more, lasting at least 1 week• inflated self-esteem or grandiosity • decreased need for sleep • more talkative than usual or pressure to keep

talking • flight of ideas or subjective experience that

thoughts are racing • distractibility increase in goal-directed activity or

psychomotor agitation • excessive involvement in pleasurable activities

that have a high potential for painful consequences

Bipolar Disorder

4% LPR -Laryngopha-ryngeal-reflux

1 in 4 or 5 commits suicide

> 55% have a history of

substance abuseMust rule out

mania caused by antidepressants, caffeine, herbals,

stimulants, corticosteroids, cough and cold preparation, diet

aids, and hyperthyroid

Bipolar DisorderMost common drugs used:• Lithium

• 28% of patients discontinue the drug• 38% experience recurrences on the

drug• Only 23% don’t have reoccurring

episodes• Valproic Acid• Antipsychotics

Lithium –a salt

• Orally (once daily due to long half life)

• Peak blood levels reach within 3 hours; crosses blood-brain barrier incompletely

• Excreted unchanged by kidneys

• Urine and skin

PharmacokineticsPharmacokineticsAbsorptionAbsorption

DistributionDistribution

MetabolismMetabolism

EliminationElimination

LithiumEffectsEffectsLess mania (though not less time to recurrence compared to placebo)

Reduction in suicidal behaviors

Nausea, vomiting, diarrhea, abdominal pain

tremor, lethargy, impaired concentration, slurred speech, ataxia, muscle weakness

Memory loss

Weight gain (depressed thyroid)

Hallucinations

Muscle rigidity, coma, renal failure, cardiac arrhythmias, and death

LithiumCaution!Caution!Illness course is believed to be worse after stopping lithium than having never received the drug (including super high suicidal behaviors and completions).

Low compliance due to side effects, high likelihood of relapse, and missing the “high”

High rate of interactions with other drugs

About 40% are either resistant to lithium or develop side effects that limit its effectiveness

Valproic Acid –antiepileptic drug

• Orally and intravenously for acute mania

• 90% bound to proteins in blood, 10% may make it to the brain (this % rises shockingly if too much is administered)

• 95% broken down by liver; with metabolites that contribute to side effects. Differences between peak and trough levels can be extreme

• Urine

PharmacokineticsPharmacokineticsAbsorptionAbsorption

DistributionDistribution

MetabolismMetabolism

EliminationElimination

Valproic AcidEffectsEffectsLess mania (though not less time to recurrence compared to placebo)

Reduction in suicidal behaviors

GI upset

Sedation

Lethargy

Hand tremor

Alopecia (loss of hair)

Metabolic changes in liver

Decreased cognitive function

Obesity (rarer side effects)

Fertility problems in women and masculinization

Valproic AcidCaution!Caution!Causes excess ammonia in the blood (hyperammonemia) which can lead to brain damage

Overdose = tremor, stupor, respiratory depression, coma, metabolic acidosis and death

Antidepressants used in treatment of bipolar disorder

• Fluoxetine (Prozac), paroxetine (Paxil), or sertraline (Zoloft) are sometimes given to people with bipolar disorder

• CAUTION: should not take an antidepressant on its own. Doing so can cause the person to rapidly switch from depression to mania

Atypical Antipsychotics Related NeurotransmittersRelated NeurotransmittersSerotonin antagonism

EffectsEffectsLess mania (depending on drug used)

More mania (depending on drug used)

Atypical Antipsychotics

Sedation (in some drugs)

Increased motor activity

Agitation

Weight gain

Extrapyramidal effects

Akathesia (sensation of inner restlessness)

Tardive dyskinesia (purposeless movements)

Schizophrenia

Symptoms2 or more for a sig. portion of time

during 1-mo. period• delusions• hallucinations• disorganized speech (e.g., frequent

derailment or incoherence, echolalia) • grossly disorganized or catatonic behavior• negative symptoms (i.e. affective flattening,

mental confusion, or lack of initiation/motivation)

Schizophrenia

Schizophrenia and the Brain Animation

1% LPR10-15% commit suicide

SchizophreniaMost common drugs used:• Typical Antipsychotics (also called

neuroleptics)- Clozapine, Thorazine, Haldol,

• Atypical antipsychotics– Risperdal, Abilify, Seroquel

Typical Antipsychotics Related NeurotransmittersRelated NeurotransmittersDopamine receptor blockage

EffectsEffectsLess positive symptoms of schizophrenia

Worse negative symptomatology of schizophrenia

Sedation

Extrapyramidal effects

Akathesia (sensation of inner restlessness)

Tardive dyskinesia (purposeless movements)

Typical Antipsychotics

Atypical Antipsychotics Related NeurotransmittersRelated NeurotransmittersSerotonin antagonism

EffectsEffectsLess positive symptoms of schizophrenia

Sedation (in some drugs)

Increased motor activity

Agitation

Weight gain

Extrapyramidal effects

Akathesia (sensation of inner restlessness)

Tardive dyskinesia (purposeless movements)

Atypical Antipsychotics

Medications for Anxiety Disorders

Anxiety disorders include: Obsessive compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Generalized anxiety disorder (GAD) Panic disorder Social phobia Fear of open and closed spaces

(agoraphobia)

Antidepressants, anti-anxiety medications, and beta-blockers are the most common medications used for anxiety disorders.

Generalized Anxiety Disorder

Symptoms 3 or more, felt most days over 6mos• Feeling wound-up, tense, or restless• Easily becoming fatigued or worn-out• Concentration problems• Irritability• Significant tension in muscles• Difficulty with sleep

Generalized Anxiety DisorderMost common drugs used:• Buspirone (Buspar)• Benzodiazepines ►

• SSRIs– Celexa, Prozac, Lexapro, Paxil, Zoloft

• SNRIs– Effexor, Pristiq, Cymbalta, Dalcipran, Meridia

Related neurotransmittersRelated neurotransmittersunknown (possible serotonin receptor agonist; possible dopamine antagonist)

Buspar (buspirone)

EffectsEffectsAnxiety remission with less withdrawal symptoms than benzos

dizziness

Headache

Lightheadedness

nausea

Excitement

Sweating/clamminess

Buspar (buspirone)

Attention Deficient Hyperactivity Disorder

Inattention Symptoms6 or more, in more than one situation +• Often does not give close attention to details or makes careless

mistakes in schoolwork, work, or other activities. • Often has trouble keeping attention on tasks or play activities. • Often does not seem to listen when spoken to directly. • Often does not follow instructions and fails to finish schoolwork,

chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions).

• Often has trouble organizing activities. • Often avoids, dislikes, or doesn't want to do things that take a lot

of mental effort for a long period of time (such as schoolwork or homework).

• Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools).

• Is often easily distracted. • Is often forgetful in daily activities.

Attention Deficient Hyperactivity Disorder

Hyperactivity SymptomsMaladaptive in more than

one situation • Often fidgets with hands or feet

or squirms in seat. • Often gets up from seat when

remaining in seat is expected. • Often runs about or climbs

when and where it is not appropriate (adolescents or adults may feel very restless).

• Often has trouble playing or enjoying leisure activities quietly.

• Is often "on the go" or often acts as if "driven by a motor".

• Often talks excessively.

Impulsivity SymptomsMaladaptive in more

than one situation • Often blurts out

answers before questions have been finished.

• Often has trouble waiting one's turn.

• Often interrupts or intrudes on others

Attention Deficient Hyperactivity Disorder

http://www.healthcentral.com/adhd/video-39189-47.html

ADHD animation

Most common drugs used:• Ritalin►

• Adderal ►

Less common drugs used• Methamphetamine ►

Attention Deficient Hyperactivity Disorder

Special Needs Groups

• Psychiatric medications are taken by all types of people, but some groups have special needs, including:– Children and adolescents– Older adults– Women who are pregnant or may become

pregnant.

Children

• Great care needs to be taken in prescribing psychotropic drugs to children

• FDA indicated that Prozac should never be used in children because of brain damage issues

• Brain is still developing and impacted more negatively than in adults

Older Adults

• Often have more medical problems

than other groups and tend to take

more medications than younger

people, including prescribed, over-the-counter, and herbal medications.

• Higher risk for experiencing bad drug interactions, missing doses, or overdosing.

• More sensitive to medications. • More likely to experience paradoxical effects

Women – pregnant or planning Research is inconsistent in

determining whether antidepressants are safe during pregnancy

Some research suggests the use of SSRIs during pregnancy is associated with miscarriage or birth defects, but other studies do not support this

Fetuses exposed to SSRIs during the third trimester may be born with "withdrawal" symptoms such as breathing problems, jitteriness, irritability, trouble feeding, or hypoglycemia (low blood sugar).

Some medications should not be taken during pregnancy.

Benzodiazepines may cause birth defects or other infant problems, especially if taken during the first trimester.

Mood stabilizers are known to cause birth defects.

Benzodiazepines and lithium have been shown to cause "floppy baby syndrome," which is when a baby is drowsy and limp, and cannot breathe or feed well.