-
Selective serotonin reuptake inhibitor
Have little blocking activity at muscarinic, alpha-adrenergic, and histaminic h1 receptors
-
The SSRI with the lowest risk of causing an SSRI discontinuation syndrome
Fluoxetine
-
Sometimes effective in relieving neuropathic pain such as diabetic peripheral neuropathy
SNRI's and tricyclics
-
Not recommended in patients with end stage renal disease
Duloxetine
-
Should not be administered in patients with hepatic insufficiency
Duloxetine
-
Is unique in that it assists in decreasing the craving and attenuating the withdrawal symptoms for nicotine
Bupropion
-
Is markedly sedating due to its antihistaminic activity, can also cause increased appetite and weight gain
Mirtazapine
-
Has been associated with causing priapism
Trazodone
-
Uncommon side effects for SSRI's
Orthostatic hypotension, sedation, dry mouth, and blurred vision
-
The TCA imipramine has been used to control
Bed wetting in children
-
The TCA amitriptyline has been used to treat
Migraines
-
Blockade of muscarinic receptors leads to
Blurred vision, xerostomia, urinary retention, constipation, and aggravation of narrow angel glaucoma
-
Blockade of alpha-adrenergic receptors leads to
Orthostatic hypotension, dizziness, and reflex tachycardia
-
Common AE of TCA
Weight gain
-
Occurs in a significant minority of patients on TCA's as compared to SSRI's
Sexual disfunction
-
TCA's should be used with caution in known manic depressives because they may
Cause manic behavior
-
Depressed patients should only be given limited quantities of TCA's because
Of their narrow therapeutic window
-
MAOI's have a ____ effect
Amphetamine like stimulant
-
MAOI's are indicated for
Patients allergic/unresponsive to TCA's
-
TCA's are an important alternative to
SSRI's
-
This limits the widespread use of MAOI's
Unpredictable side effects due to food and drug interactions
-
Considered a mood stabilizer, it is not a sedative, euphoriant, or depressant
Lithium salts
-
Patients with personality disorders tend to show ___ when pathological coping mechanisms fail
Anxiety and depression
-
The more severe cases of personality disorder can decompensate into __ under stress
Psychosis
-
The best predictor of death by suicide
Previous attempt
-
Paranoia is a warning sign for
Violence
-
Acute psychosis, suicidality, violence, and mania are all considered
Types of psychiatric crises
-
No improvement (despite treatment), psychiatric co-morbidities, suicidal or homicidal (serious or continuing), questions about drug therapies, time and expertise (more needed to resolve problems than you can provide)
When to make a mental health referral
-
Anxiety
a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry
-
Generalized anxiety disorder
Characterized by excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry. This excessive worry often interferes with daily functioning
-
Cognitive behavioral therapy
Is a psychological method of treatment for GAD, which involves a therapist working with the patient to understand how thoughts and feelings influence behavior. The goal of the therapy is to change negative thought patterns, replacing them with positive ones
-
Panic disorder
Characterized by recurring severe attacks. It may also include significant behavioral change lasting at least a month, and of ongoing worry about the implications or concern about having other attacks
-
Obsessive compulsive disorder
Characterized by intrusive, repetitive thoughts resulting in compulsive behaviors and mental acts that the person feels driven to perform, according to rules that must be applied rigidly, aimed at preventing some imagined dreaded event
-
Obsession
Recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and that cause marked anxiety or distress. The thoughts, impulses, or images are not simply excessive worries about real-life problems
-
Compulsion
Repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly. The behaviors or mental acts are aimed at preventing or reducing distress or preventing disaster
-
Anxiety disorder that can develop after exposure to one or more terrifying events that threatened or caused grave physical harm. It is a severe and ongoing emotional reaction to an extreme psychological trauma
Post traumatic stress disorder
-
Excessive social anxiety (anxiety in social situations) causing abnormally considerable distress and impaired ability to function in at least some areas of daily life
Social phobia
-
Irrational, intense, persistent fear of certain situations, activities, things, or people. The main symptom of this disorder is the excessive, unreasonable desire to avoid the feared subject.
Phobia
-
External signs of __ may include pale skin, sweating, trembling, and pupillary dilation
Anxiety
-
Can be accompanied by physical effects such as heart palpitations, fatigue, nausea, chest pain, shortness of breath, stomach aches, or headaches
Anxiety
-
Neural circuitry involving the amygdala and hippocampus is thought to underlie
Anxiety
-
Choices of treatment for __ include psychotherapy (such as cognitive behavioral therapy); lifestyle changes; or pharmaceutical therapy (medications).
Anxiety
-
Meta-analysis indicates that psychotherapeutic interventions have superior long-term efficacy when compared to pharmacotherapy for treatment of
Anxiety
-
Is a mental disorder characterized by a pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities
Major depression
-
Mood disturbance of at least 2 weeks' duration, with between two and five symptoms of depression
Minor depression
-
Is a mood disorder that falls within the depression spectrum. It is considered a chronic depression, but with less severity than major depressive disorder.
Dysthymia
-
A mild, reactive, depression which last only a few months. The disorder occurs in response to some specific stressful situation or circumstance.
Adjustment disorder with depressed mood
-
A brain disorder that causes unusual shifts in a person’s mood, energy, and ability to function
Bipolar disorder
-
A severe medical condition characterized by extremely elevated mood, energy, unusual thought patterns and sometimes psychosis.
Mania
-
__ is characterized by persistent and pervasive elevated or irritable mood. People experiencing __ symptoms typically have a flood of ideas, and sometimes mildly grandiose thoughts and visions
Hypomania
-
Is a mood disorder; a very mild form of bipolar disorder
Cyclothymic disorder
-
Markedly diminished interest or pleasure in almost all activities, reported or observed
Anhedonia
-
Major depressive episode mnemonic: Sig e caps(s)
Sadness, interest, guilt, energy, concentration, appetite, psychomotor activity, sleep, suicide
-
Symptoms of a major depressive episode must last at least __ weeks
2
-
DIGFAST (mania mnemonic)
Distractibility, insomnia, grandiosity, flight of ideas, activities, speech, thoughtlessness
-
Obstructive sleep apnea may cause __
Executive dysfunction, impaired vigilance, and depression
-
__ is more predominant in depressed men than depressed women
Substance abuse
-
Insomnia increases the risk of depression __ times
4
-
Involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration
Vaginismus
-
Inflammation at the entrance of the vagina characterized by a burning sensation
Vestibulitis
-
Vaginismus, vestibulitis
Dyspareunia
-
Compulsive masturbation, fetish, transvestism
Paraphilia
-
Characterized by shame, and secretiveness, not interactive, not transferable to partner sex
Variant arousal patterns
-
Implies that the belief is pathological (the result of an illness). As a pathology it is distinct from a belief based on false or incomplete information or certain effects of perception which would more properly be termed an apperception or illusion.
Delusion
-
Paranoid, grandiose, religious, nihilistic, somatic
Types of delusions
-
Thought insertion, thought withdrawal, thought broadcasting, ability to read, others’ thoughts, ideas of reference
Delusions: Schneider’s “first rank symptoms”
-
Do you feel that others can read your thoughts?
Thought broadcasting
-
Is the person on TV/radio sending you special messages or talking directly about you. Do things out in the public relate to you in a unique way?
Ideas of reference
-
Behaviors that have no explanation, the patient doesn't know why they are doing it. Present in psychosis
Automatisms
-
Blunted or flat, bizarre, incongruent with content
Abnormalities of affect associated with psychosis
-
Substance induced and due to general medical condition
2 most common causes of psychosis
-
Schizophrenia affects __% of the population worldwide
1
-
Typical onset of schizophrenia is __
Late teens to early 20's
-
Hallucinations, delusions, disorganized speech and behavior, agitation, respond fairly well to conventional antipsychotic medications.
Positive symptoms of schizophrenia
-
Avolition, withdrawal/autism, anhedonia, blunted affect, poverty of speech, may respond somewhat better to ‘atypical’ antipsychotic medications.
Negative symptoms of schizophrenia
-
Choreoathetoid movements (irregular, writhing), may involve tongue, cheeks, lips, trunk, extremities, develops after months to years of antipsychotic med use in up 25% in patients on chronic therapy. May be irreversible.
Tardive dyskinesia
-
Akathisia, acute dystonias, parkinsonism
Acute extrapyramidal effects of antipsychotics
-
Subjective inner restlessness
Akathisia
-
Bradykinesia, shuffling gait, regular resting tremor
Parkinsonism
-
A psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking
Schizophrenia
-
Negative symptoms of __ are so-named because they are considered to be the loss or absence of normal traits or abilities
Schizophrenia
-
In the united states, __ million females and 1 million males are struggling with an eating disorder such as anorexia or bulimia
10
-
__ has the highest mortality rate of all psychiatric illnesses
Anorexia nervosa
-
Refusal to maintain body weight at or above minimum (85% of expected given age, height, intense fear of gaining weight, disturbance in the way body weight, size, or shape is experienced
Anorexia nervosa
-
__ can cause amenorrhea >= 3 months
Anorexia nervosa
-
Life time prevalence of anorexia nervosa is as high as __%
3.7
-
Approximately __% of those with anorexia nervosa are female
90-95%
-
Recurrent episodes of binge eating, eating large quantities of food in discrete period, sense of lack of control
Bulimia nervosa
-
In bulimia nervosa behaviors occur at least __ times per week for 3 months
2
-
These patients tend to maintain a normal weight
Bulimia nervosa
-
The two types of bulimia nervosa are
Purging and non-purging
-
When anorexia nervosa is suspected you need to specify between
Restricting behaviors and binge-eating/purging
-
Cardiac arrhythmias, esophageal, inflammation, tear, tooth decay and staining, vagus nerve irritation, loss of bowel elasticity, motility, gastric rupture possible, and are health consequences of
Bulimia nervosa
-
__% of those with bulimia nervosa are female
80
-
Frequent episodes of eating large quantities of food in short periods of time, feeling out of control over eating behavior, feeling ashamed or disgusted by the behavior. Eating when not hungry and eating in secret.
Binge eating disorder
-
High blood pressure, high cholesterol levels, heart disease, diabetes mellitus, gallbladder disease
Binge eating disorder
-
__% of those with binge eating disorder are female
60
-
__ has the greatest stability over time and considerably worse long-term outcome
Anorexia nervosa
-
Anxiety (OCD, social phobia, GAD), depression, AXIS II (anxious-fearful cluster) emotional-dramatic cluster
Common comorbidities of eating disorders
-
Individual’s mood has been depressed for two or more weeks or person has had anhedonia for over two weeks.
Major depression:
-
Individual has had chronically depressed mood for at least 2 years. Two other associated depression symptoms when person has the depressed mood.
Dysthymic disorder
-
Individual has at least one week of mania. Manic episode is a persistently elevated, expansive, or irritable mood with 3 or more: inflated self-esteem or grandiosity, decreased need for sleep, more talkative, agitated, goal-directed, thoughts racing
Bipolar disorder type I
-
A distinct period during which there is an abnormally and persistently elevated, expansive or irritable mood that lasts at least 4 days.
Hypomanic episode
-
Bipolar disorder type II (recurrent major depressive episodes with hypomanic episodes)
Bipolar disorder type II
-
During the period of pts mood disturbance, 3+ of these sx present: inflated self-esteem or grandiosity, decreased need for sleep, more talkative, agitated, goal-directed, thoughts racing, distractible, excessive danger-pleasure involvement
Bipolar disorder type II
-
Is a chronic mood disturbance with episodes of depression and hypomania.
Cyclothymia
-
Symptoms must have at least a 2-year duration and are milder than those that occur in depressive or manic episodes.
Cyclothymia
-
Manifestations include depressed mood, tearfulness, or feelings of hopelessness. Disorder occurs within 3 months of the stressor and causes impairment in functioning.
Adjustment disorder with depressed mood
-
Is a psychological response to an identifiable stressor that result in clinically significant symptoms.
Adjustment disorder
-
Respondent with lifetime MDD also met the criteria for >1 other DSM-IV disorders: with anxiety disorder; with substance use disorder; with impulse control disorder
Major depression: psychiatric co-morbidities
-
Increased risk of hypertension; CVA; CAD; risk of death after mi; mechanisms: increase HPA activation, sympatho-medullary activity, platelet aggregation; coagulation; decrease fibrinolysis, heart rate variability
Major depression: in CAD
-
After a mi, patients with depression have a 3.5-fold increase in cardiovascular mortality relative to patients without depression
Major depression: in CAD
-
Increase non-adherence, hba1c, retinopathy; neuropathy; nephropathy macrovascular complications
Major depression: in diabetes
-
Nine item brief self-report developed for primary care. Items from DSM-IV-TR signs/sx of MDD. Use for provisional dx and tx monitor
PHQ-9
-
Restricting type or binge-eating/purging type
Anorexia nervosa
-
Purging type or non-purging type
Bulimia nervosa
-
Has a mortality rate of 5-20%.
Anorexia nervosa
-
Secrecy about and preoccupation with food and eating behaviors. Concerns about body weight and image. Self-esteem issues. Denial
Common characteristics of eating disorders
-
Influenced by chemical imbalances. Serotonin. SSRIs have been shown to be helpful. A biologically mediated affective disorder.
Bulimia
-
Distorted body image. Intense fear of becoming overweight. Weight loss to 15% below ideal body weight. Amenorrhea. Absence of at least 3 consecutive periods.
Anorexia nervosa
-
Engages in binge eating or purging behaviors. Laxatives. Vomiting. Diuretics. Enemas
Binge eating type: anorexia nervosa
-
Self-starvation
Restrictive type: anorexia nervosa
-
Preoccupied with food. Rituals. Cooks for others only. Social withdrawal. Exercises obsessively. Weighs frequently. Fatigue. Loss of hair. Stops menstruating. Sensitivity to cold.
Signs and symptoms of anorexia nervosa
-
Death. Starvation/arrhythmia. Dehydration. Renal symptoms. Electrolyte abnormalities. Malnutrition. Amenorrhea. Hypotension. Bradycardia. Reduced bone density. Fractures. Hypothermia. Fainting and chronic fatigue. Lanugo – fine hair growth on body.
Complications of anorexia nervosa
-
Recurrent episodes of binge eating. Lack of control. Constant body image dissatisfaction. Inappropriate compensatory behavior in order to prevent weight gain. Min. 2/wk for 3 months.
Bulimia
-
Purging: laxatives, vomiting, diuretics, enemas. Non-purging: fasting, excessive exercise, prevent weight gain.
Bulimia
-
Engages in binge eating and cannot. Voluntarily stop. Followed by purging and sense of relief. Reacts to emotional stress by overeating. Experiences frequent. Fluctuations in weight. Feels guilty or ashamed about eating. Has depressive moods.
Symptoms bulimia nervosa
-
Death, dehydration and malnutrition, electrolyte abnormalities, hypotension and bradycardia, heart failure, parotiditis, chipmunk cheeks. Tooth decay. Irregular bowel motility due to loss of bowel elasticity. Esophageal inflammation and rupture risk.
Complications of bulimia nervosa
-
Must have at least 3: eating more rapidly than normal. Eating till uncomfortably full. Eating food when not hungry. Eating alone b/c of embarrassment. Feeling disgusted, depressed, or guilty after overeating. 2 or more days/week for 6 month period.
Binge eating disorder
-
Unlike bulimia: binge eating happens in episodes and is not constant. No purging behaviors.
Binge eating disorder
-
Unlike anorexia: ashamed of behavior. Like anorexia: eating in secret.
Binge eating disorder
-
Obesity, high blood pressure, high cholesterol, heart disease, diabetes mellitus, gall bladder disease
Complications of binge eating disorder
-
Most common diagnosis among eating disorders. Issues around food and body weight. Food diaries. Do not fit criteria for other disorders. Secrecy. Difficult to establish trust. Loss to follow up. Denial
Eating disorder nos
-
Treatment of choice for anorexia nervosa:
Maudsley family therapy
-
Treatment of choice for bulimia nervosa
Cognitive behavioral therapy or interpersonal therapy.
-
Acceptance and mindfulness along with commitment and behavior change strategies.
Acceptance and commitment therapy (act)
-
Biggest challenge in an treatment:
Ego-syntonic nature of the symptoms.
-
Biggest challenge in BN and BED treatment
Shame and embarrassment.
-
-
Potentially fatal condition. Rapid changes in fluids and electrolytes. Malnourished patients that are given oral, enteral or parenteral feedings.
Re-feeding syndrome
-
At risk patients: severe anorexia nervosa, <75%ile of ideal body weight. Lost a large amount of weight rapidly. Prolonged weight loss.
Re-feeding syndrome
-
Defined primarily by manifestations of severe hypophosphatemia: cardiovascular collapse, rhabdomyolysis, seizures, delirium, malnourished patients can have depleted intracellular phosphate stores.
Re-feeding syndrome
-
With re-feeding there is a shift from fat to carbohydrate metabolism. Hypokalemia results from insulin secretion in response to caloric load. Shifts potassium into cells. Hypokalemia can lead to arrhythmias. Risk of
- Wernicke’s encephalopathy.
- Re-feeding syndrome
-
Can result in impaired energy stores due to depletion of intracellular ATP and tissue hypoxia
Hypophosphatemia
-
Dramatic increase in food preoccupations and odd eating behaviors/rituals. Strong emotional reactions around food. Binge eating followed by regret and self-disgust. Emotional changes: irritability, anxiety, apathy, depression or suicidality, psychosis
Effect of starvation
-
Disordered eating, menstrual dysfunction, osteoporosis
Female athletic triad
-
The prevailing, underlying emotional tone; it is also what the patient feels
Mood
-
The objective, observed component of emotion. It is also the variability of emotion as thoughts change.
Affect
-
Allow the patient to give spontaneous responses. Give control to the patient. Not time-efficient. Combine open and closed questions.
Open-ended questions
-
Naming the emotion you see and reflecting it back to the patient
Reflective listening
-
Gestures or words that encourage communication, but don’t lead the patient.
Facilitation
-
Implies an understanding of the patient’s feelings (doesn’t necessarily imply agreement). Gives patient feeling of being supported.
Legitimization
-
The process of moving as the other person moves as a means of acknowledging the other’s behavior and reflecting their emotional state.
Matching: non-verbal communication
-
Facial expressions, gestures, touch, position, body tension
Kinesics: non-verbal communication
-
Spatial relationships and barriers
Proxemics: non-verbal communication
-
Voice tone, rhythm and rate, volume, emphasis
Paralanguage: non-verbal communication
-
Flushing, sweating, changes in breathing and pupil size, dry mouth
Autonomics: non-verbal communication
-
A change in a patient’s condition attributable to the symbolic import or therapeutic intent of a treatment.
The placebo effect
-
Clinical disorders” (most psychiatric disorders, and other psychiatric conditions that are a focus of clinical attention) including schizophrenia.
AXIS I
-
Personality disorders and R
AXIS II
-
General medical conditions.
AXIS III
-
Psychosocial and environmental problems.
AXIS IV
-
Global assessment of functioning.
AXIS V
-
Cluster A
Schizotypal, schizoid, paranoid
-
Cluster B
Antisocial, histrionic, borderline, narcissistic
-
Cluster C
Anxious-fearful: avoidant, dependent, obsessive-compulsive
-
An event is experienced as overwhelming. Psychological symptoms are triggered. Physical symptoms are triggered
Psychiatric crises
-
Feelings patient has for you
Transference
-
Feelings for your patients
Countertransference
-
Sense of self as a male or a female. Established by about 18 mo of age
Gender identity
-
Concept that boys become men and girls become women. Established between 18 mo and 30 mo
Gender stability
-
Immutability of one's gender. Is firmly established and resistant to change by 30 mo
Gender constancy
-
Public behaviors commonly thought to be associated with maleness or femaleness (within a culture)
Gender role
-
A strong, persistent discomfort (dysphoria) with one's anatomic gender coupled with persistent cross-gender identification.
Gender identity disorder
-
Reassure that questions are a routine part of clinical practice and preventive care
Inclusion
-
Communicate to the patient that these experiences are quite prevalent and that she or he is not alone.
Normalization
-
Phrase questions as if everyone has done everything, which makes answering in the affirmative easier for potentially sensitive questions.
Universalization
-
Refers to recurrent or persistently deficient sexual fantasies or desire for sexual activity that causes personal distress or interpersonal difficulty
Hypoactive sexual desire disorder
-
Usually refers to the avoidance of, or aversion to, all or nearly all genital (or other, e.g., breast) sexual contact with a partner. Must also cause distress or difficulty to be considered a disorder.
Sexual aversion disorder
-
The inability for a male to achieve an erect penis as part of the overall multifaceted process of male sexual function
Erectile dysfunction
-
Refers to pain experienced immediately before, during, or after intercourse by women or men.
Dyspareunia
-
Is usually caused by insufficient lubrication or spasm of the anal musculature
Anal dyspareunia
-
Defined in the DSM-IV as the inability to attain or maintain a genital lubrication-swelling response during sexual activity divided into subjective, genital, and combined subtypes .
Female sexual arousal disorder
-
Orgasmic dysfunction refers to the inability to reach orgasm when desired.
Female orgasmic disorder
-
In which the patient has never experienced orgasm
Primary inhibited orgasm
-
In which the dysfunction manifests after previous satisfactory orgasmic functioning
Secondary inhibited orgasm
-
Involuntary, usually painful, spastic contraction of the pelvic musculature surrounding the outer third of the vagina.
Vaginismus
-
Severe pain on vestibular touch or attempted vaginal entry. Tenderness to pressure localized within the vulvar vestibule. Physical findings confined to vestibular erythema, etiology currently unknown
Vulvar vestibulitis
-
Refers to pain experienced immediately before, during, or after intercourse by women or men
Dyspareunia
-
Severe breakdown of mental functioning with impaired contact with reality
Psychosis
-
Loosening of associations, poverty of thought, thought blocking, mutism
Thought disorder
-
New invented idea speech
Neologisms
-
-
Sensory stimuli that is misinterpreted
Illusions
-
No external stimulation, visual is most common
Hallucinations
-
Fixed, bizarre, unrealistic beliefs. Not subject to rational argument. Not accounted for by accepted cultural or religious beliefs. Patient may conceal.
Delusions
-
General mistrust or suspiciousness. Plausible but false beliefs. Bizarre delusions. Elaborate delusional systems
Paranoid delusions
-
Paranoid. Grandiose. Religious. Nihilistic. Somatic. Referential
Types of delusions
-
Hallucinations. Delusions. Disorganized speech and behavior. Agitation. Respond fairly well to conventional antipsychotic medications.
Positive symptoms of schizophrenia
-
Avolition. Withdrawal/autism. Anhedonia. Blunted affect. Poverty of speech. May respond somewhat better to ‘atypical’ antipsychotic medications.
Negative symptoms of schizophrenia
-
On AXIS, clinician rates the person's level of functioning both at the present time and the highest level within the previous year. This helps clinician understand how the other axes are affecting the person and what type of changes could be expected.
AXIS v: highest level of functioning
-
Events in a persons life, such as death of a loved one, starting a new job, college, unemployment, and even marriage can impact the disorders listed in AXIS I and II. These events are both listed and rated for this AXIS.
AXIS Iv: severity of psychosocial stressors
-
Which play a role in the development, continuance, or exacerbation of AXIS I and II disorders, physical conditions such as brain injury or HIV/AIDS that can result in symptoms of mental illness are included here.
AXIS III: physical conditions
-
Developmental disorders include autism and mental retardation, disorders which are typically first evident in childhood personality disorders are clinical syndromes. They include paranoid, antisocial, and borderline personality disorders.
AXIS II: developmental disorders and personality disorders
-
This is what we typically think of as the diagnosis (e.g., depression, schizophrenia, social phobia)
AXIS I: clinical syndromes
-
A feeling of nervousness or worry”. “a complex set of psychobiological responses to perceived danger or threat”
Anxiety
-
In response to threat, heightened alertness, concentration, readiness for muscle action, reduced GI function, “fight-or-flight”
An adaptive response to anxiety
-
Benign stimuli perceived as threat. Response is exaggerated, self-perpetuating, impairs ability to function
A maladaptive response to anxiety
-
The most prevalent psychiatric disorders in the us
Anxiety disorders
-
A reaction to stress: causes of stress are different at different ages. Reactions include anxiety and depression, avoidant behavior. Maladaptive behavior is called adjustment disorder. Does not meet criteria for other “major” types of anxiety disorders
Adjustment disorder with anxious mood
-
Treatment: psychological, stress reduction techniques, daily log, relaxation exercises, CBT. Pharmacological: sedatives (benzodiazepines), danger of addiction
Adjustment disorder with anxious mood
-
Disabling condition commonly seen in primary care. Patients suffer from attacks with rapid onset of symptoms and persistent concern about having an attack. Can occur one to several times per week, usually unpredictably. Frequency of attacks wax and wane.
Panic disorder
-
Fear of open spaces or of being in crowded, public places or leaving a safe place
Agoraphobia
-
Fear of situations that may involve scrutiny or judgment by others
Social phobia
-
A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes
DSM-IV criteria for panic attack
-
Felt to be due to phobia of internal sensations. Drives avoidance behavior. Cognitive model suggests patents misinterpret thoughts and emotions as physical symptoms. Alternate theory that benign body sensations spiral into panic attacks
Panic disorder
-
Antidepressants plus CBT. Antidepressants SSRIs and TCAs are equally effective in reducing severity and number of attacks
Panic disorder
-
Classified as a disorder without panic attacks or symptoms of depression
Generalized anxiety disorder
-
Excessive physiologic arousal, distorted cognitive processes, poor coping strategies
Generalized anxiety disorder
-
Highest prevalence of all anxiety disorders
Generalized anxiety disorder
-
Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least six months, about a number of events or activities (such as work or school performance). The person finds it difficult to control the worry
DSM diagnostic criteria: GAD
-
Relaxation and biofeedback to decrease arousal. Cognitive therapy to limit distortions and make better plans to manage anxiety. Benzodiazepines. Serax (oxazepam) Klonopin (clonazepam)
GAD treatment
-
For those with chronic anxiety and those who relapse after benzodiazepine therapy
BuSpar
-
Arises following exposure to perceived life-threatening trauma. Symptoms can mimic that of anxiety or depressive disorders. Symptoms may be transient, may take longer than 6 months to appear, and may last a lifetime
Post-traumatic stress disorder (PTSD)
-
Has exposed to traumatic event which: experienced, witnessed, or confronted with event that involved actual/threatened serious injury, or a threat to the physical integrity of self or others. Person’s response involved intense fear, helplessness or horror
DSM diagnostic criteria: PTSD
-
Similar to PTSD in that it occurs after exposure to a traumatic event. Appears within 4 weeks of trauma. Fewer symptoms required to make diagnosis. More dissociative symptoms (“in a daze,” temporary amnesia).
Acute stress disorder (ASD)
-
PTSD treatment
SSRI. Goal is to break pattern of self-defeat by reexamining the traumatic event and the response to it. Education and recognition of cues are key
-
Social anxiety disorder
- An intense, irrational and persistent fear of being scrutinized or negatively evaluated by others
- Feared situations are avoided or else are endured with intense anxiety or distress
- The avoidance, anxious anticipation, or distress in the feared performance situation(s) interferes significantly with the person’s normal routine, occupational functioning, or social activities or relationships, or there is marked distress
- Marked and persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others
- Exposure to the feared social situation almost invariably provokes anxiety, which may take the form of a situationally bound or situationally predisposed panic attack
-
Treatment social anxiety disorder
SSRIs (Paxil, Luvox, Zoloft, and Celexa) and MAOIs are effective. Benzodiazepines can also be effective but may relapse after discontinuation. And CBT.
-
Characterized by recurrent distressing thoughts and repetitive behaviors or mental rituals performed to reduce anxiety. Feelings of shame and secrecy
Obsessive-compulsive disorder (OCD)
-
Involvement of the dorsolateral prefrontal cortex, basal ganglia, and thalamus. Thought that serotonin system is heavily involved
OCD
-
Obsessions and compulsions are severe enough to be time consuming (more than 1 hour daily) or to cause marked distress or significant impairment
OCD
-
Treatment OCD
CBT & SSRIs are first line
-
Short-term goals: reduce severity and duration of symptoms; improve functioning
Generalized anxiety disorders (GAD)
-
Long-term goals: achieve symptom remission facilitate patient’s return to pre-morbid level of functioning. Reduce length of episodes. Reduce severity of episodes & prevent recurrence
Generalized anxiety disorders (GAD)
-
Benzodiazepines
First-line treatment GAD
-
Selective serotonin reuptake inhibitors (SSRIs)
First-line treatment GAD
-
Selective norepinephrine reuptake inhibitors (SNRIs)
First-line treatment GAD
-
Buspirone (BuSpar)
GAD treatment
-
Hydroxyzine, imipramine, and propranolol
GAD treatment
-
Located in every region of the brain. Consists of GABAA and GABAB receptors
⋎- aminobutyric acid (GABA)
-
Receptors produce inhibitory effect on CNS
GABA-a receptors
-
Receptors produce inhibitory effect on GABA release
GABA-b receptors
-
Chloride ion channel open and influx of chloride ions. Hyper-polarization and reduced firing of the neuron
GABA-a receptors
-
Expression of receptors may fluctuate over time and in response to stress
GABA receptors
-
Potentiates inhibitory effect of GABA. Bz-GABA receptor complex. Binds of benzodiazepines coupled with GABA binding. Increases the opening of the chloride ion channel
Benzodiazepines
-
Varying degrees of lipophilicity. Affects ability to cross the blood-brain barrier. May produce rapid onset of action. Experience rush of euphoria. Unpleasant feeling/loss of control
Side effects of benzodiazepines
-
CNS depression; impairment of memory or recall; abuse (unlikely in general population), dependence
Side effects of benzodiazepines
-
Patients with liver dysfunction. Slower onset of effect
Lorazepam and oxazepam
-
Non-compliance, avoidance of withdrawal symptoms
Diazepam
-
Treatment of choice for acute anxiety relief. Produce effects within days to one week. Produce additional benefit on sleep and muscle relaxation
Benzodiazepines
-
Immediate return of original symptoms, sometimes with higher intensity. Usually seen with bz
Rebound symptoms
-
Common symptoms: anxiety, restlessness, insomnia, agitation, muscle tension, irritability
Withdrawal symptoms in bz
-
Partial agonist at 5-ht1a pre- and post-synaptic receptors. Stimulation of pre-synaptic somatodendritic 5-ht1a autoreceptor allows 5-ht repletion. Stimulation of post-synaptic 5-ht1a produces anxiolytic effect
Mechanism of action of buspirone
-
Lack of sedation and anxiolytic properties are major advantages. Dizziness, nausea, and headache. Minimal drug interactions
Buspirone side effects
-
Metabolized by cyp3a4
Buspirone
-
Use in GAD. Current/history of substance abuse. Intolerant to by therapy. Refractory GAD. Less sedation and functional impairment than by
Buspirone
-
Vistaril, Atarax
Hydroxyzine
-
Potent antihistanergic, anticholinergic, and antispasmodic effects
Mechanism of action: hydroxyzine (Vistaril, Atarax)
-
GI, headache, sedation, and minimal drug interactions
Side effects: hydroxyzine (Vistaril, Atarax)
-
Blocks reuptake of 5-ht and ne
Mechanism of action: imipramine (Tofranil)
-
Anticholinergic, sedative, cardiovascular, and CNS
Side effects: imipramine (Tofranil)
-
-
Moa (anxiolytic): blockade of postsynaptic beta receptors results in decrease of autonomic symptoms
Beta blockers in GAD
-
Use in GAD. Good for patients with prominent CV symptoms (palpitations, tremors). Adjunctive therapy for refractory GAD
Beta blockers in GAD
-
Antidepressants: SSRI’s; venlafaxine (Effexor); mirtazapine (Remeron), TCAMAOI, benzodiazepines (2nd line), alprazolam, clonazepam
Panic disorder
-
Venlafaxine, mirtazapine, trazodone
SSRI’s
-
-
Clomipramine, nortriptyline, desipramine
TCA
-
-
Second line therapy due to drug-drug and drug-food interactions. Reserved for refractory cases
MAOI
-
Only by with FDA approval for panic disorder
Alprazolam
-
CBT
Cognitive behavioral therapy
-
CBT first-line for mild cases. CBT + SSRI for severe cases (may try SSRI alone in adults). Clomipramine for 2-3 failed SSRI trials. If concomitant depression, psychosis or mania present, treat those first.
OCD
-
Affects both ne and 5ht, potent 5ht effects treat OCD. Lots of se
TCA
-
H1 - sedation, weight gain. M1 - dry mouth, blurred vision, tachycardia, constipation, urinary retention, confusion. Alpha1 - oh, dizziness. CV - conduction disturbances, seizures. Sexual dysfunction
Side effects of clomipramine
-
H/o liver disease: LFTs. Fever and sore throat. CBC to check for agranulocytosis cg - clomipramine in patients > 40yoelicit side effects via questioning at each outpatient appointment (usually once a week to every 3 months)
Clomipramine
-
Incorrect diagnosis, inadequate treatment, wrong drug, dose too low, length of therapy too short, no behavioral therapy, poor compliance
Reasons for therapy failure
-
Substantia nigra innervating the caudate nucleus, putamen. Controls voluntary movement
Nigrostriatal pathway (a9)
-
D2 receptor blockade causes extrapyramidal symptoms (eps). Increased activity may be associated with positive symptoms.
Nigrostriatal pathway (a9)
-
D2 receptor blockade causes
Extrapyramidal symptoms (eps)
-
Increased activity of nigrostriatal pathway may be associated with
Positive symptoms
-
Midbrain ventral tegmentum innervating limbic area structures. Integrates emotions with sensorimotor functions. Arousal, memory, stimulus processing, motivation
Mesolimbic pathway
-
Hyper da activity produces positive symptoms. Blockage of da receptors relieves psychosis
Mesolimbic pathway
-
Hyper da activity produces
Positive symptoms in schizophrenia
-
Blockage of da receptors relieves
Psychosis schizophrenia
-
Midbrain ventral tegmentum innervating frontal/prefrontal cortex
Mesocortical da pathway
-
Integrates executive functioning, thinking, and memory, cognition, communication, social functioning, stress
Mesocortical da pathway
-
Hypo da activity leads to negative symptoms. Blockade of da receptors relief of psychosis. May increase negative symptoms
Mesocortical da pathway
-
Hypo da activity leads to
Negative symptoms in schizophrenia
-
Hypothalamus innervating anterior pituitary gland. Integrates release of prolactin
Tuberoinfundibular da pathway
-
Blockade of d2 receptors increases in prolactin levels
Tuberoinfundibular da pathway
-
Receptors found in all 4 da tracts
D1 and d2 receptors
-
Blocking d2 in mesolimbic pathway produces
Antipsychotic effect
-
Cognition and emotion. D3 and d4 receptors found in the
Mesolimbic pathway
-
Found in hippocampus, hypothalamus, and thalamus. Affective, neuroendocrine, and pain symptoms.
D5 receptors
-
Hypofunction/expression of NMDA receptors. Symptoms similar to da hyperactivity
Role of glutamate
-
Antipsychotics may increase
Glutamatergic transmission
-
Dysfunction produces changes in mood, appetite, sleep, thermoregulation, attention, and motor behavior
Role of 5-ht
-
Lessen eps in nigrostriatal pathway. Lessen negative symptoms in prefrontal cortex
Antagonism of 5-ht2 receptors blocks inhibition on da
-
First episode psychosis
Atypicals
-
Noncompliance
Long-acting medications
-
Aggression
Clozapine. High potency typical. Olanzapine and quetiapine
-
Insomnia
Olanzapine, quetiapine. Low potency typicals
-
-
Suicidal behavior
Atypicals
-
Substance abuse
Atypicals
-
Cognitive problems
Atypicals
-
Compulsive water drinking
Clozapine
-
Predictors of good treatment response
Previous response to treatment. Acute onset. Short duration of illness. Presence of acute stressors. Later age of onset. Family history of affective illness. Good pre-morbid levels of social functioning.
-
Predictors of poor treatment response
Extreme negative or cognitive symptoms. Poor initial treatment response. Even if conditions optimized pts. Still negative towards therapy.
-
Blockade highest with low potency typicals
Cholinergic receptors & histaminergic receptors
-
Low potency typicals. High affinity for 5-ht2 receptors. Clinical doses produce saturation of these receptors
Chlorpromazine
-
Main feature of atypicals is
Diminished eps and prolactin levels
-
Attach at the same rate to the d2 receptor as typicals. Quick rate of dissociation from the d2 receptor. Fast dissociation increases response to phasic bursts of da. Modulation of the da signal without disruption.
- Da receptors
- Increased ratio of 5-ht to da blockade. Low doses produce significant blockade
-
5-ht receptors
Only true atypical antipsychotic
-
Clozapine
Diminished eps due to high anticholinergic properties. D2 blockade increased eps, akathisia
-
Olanzapine
Blocks alpha-1, h1
-
Risperidone
Lowest d2 binding of all antipsychotics. Diminishes with time from last dose, undetectable at 12hrs
-
Quetiapine
Inhibits reuptake of ne and 5-ht
-
Ziprasidone
Partial agonist activity at d2 and 5-ht1a receptors. Antagonist activity at 5-ht2a
-
Aripiprazole
Muscle spasms. Jaw, tongue, neck. Increases in da release. Hypersensitivity of da receptors.
-
Dystonia
Treatment: acute: stop offending medication; start anticholinergics or benzodiazepines at lower dose: start prophylactic therapy. Switch to atypical
-
Dystonia
Subjective restlessness. Objective inability to be still. Da blockade. Increase in motor activity. Dysfunction of ne
-
Akathisia
Treatment: start at low dose or decrease dose. Switch to an atypical agent. Clozapine. Anticholinergics are ineffective. Benzodiazepines/beta-blockers. Propranolol
-
Akathisia
Impulsive/violent behavior. High risk for suicide.
-
Akathisia
Four cardinal symptoms: akinesia, bradykinesia. Pill rolling tremor. Cogwheel rigidity. Shuffling gait. Masked facies. Imbalance of da/ach
-
Pseudoparkinsonism
Treatment: anticholinergics. Benztropine. Trihexyphenidyl. Diphenhydramine
-
Pseudoparkinsonism
BLM: first detectable sign fly catchers tongue, puckering, facial movements, grimacing, chewing. Truncal movements: rocking, gyrating. Upper and lower extremities: fast/slow, irregular, purposeless, spontaneous movements. Foot tapping
-
Tardive dyskinesia
Hypersensitivity of da receptors in nigrostriatal pathway. Imbalance of da/ach. Decreased da decreases GABA inhibition. GABA-enhancing drugs ineffective. Role of free-radicals, ne, and 5-ht
-
Tardive dyskinesia
Risk factors: high doses, long length of therapy, cumulative therapy, increased age, organic mental disorder, diabetes mellitus, mood disorder, female gender
-
Tardive dyskinesia
Treatment: switch to atypical. Risperidone, olanzapine/quetiapine; clozapine; vitamin e
-
Tardive dyskinesia
Autonomic instability: tachycardia, labile blood pressure, sweating, tachypnea, incontinence. Muscle rigidity. Altered consciousness
-
Neuroleptic malignant syndrome (NMS)
Abnormal labs: temperature > 38°c; creatine kinase; myoglobinuria; AST/ALT; WBC with/out left shift
-
Neuroleptic malignant syndrome (NMS)
Da blockade: hypothalamus: disruption of thermoregulatory process; increase heat production due to increased muscle contraction. Nigrostriatal pathway: increased rigidity and eps
-
Disruption of thermoregulatory process. Increase heat production due to increased muscle contraction.
Hypothalamus
-
Increased rigidity and eps
Nigrostriatal pathway
-
Clozapine, quetiapine, risperidone
Cardiovascular side effects of antipsychotics
-
Low-potency typicals; quetiapine, risperidone, clozapine
Tachycardia: combination of anticholinergic effects, orthostatic hypotension, and elevated norepinephrine levels
-
ECG changes: antiarrhythmic or arrhythmogenic. Bind to ikr (k+ rectifier). Involved in repolarization. Torsades de pointes
Haloperidol iv, thioridazine, mesoridazine, ziprasidone
-
Clozapine and olanzapine; risperidone; quetiapine
Weight gain side effects antipsychotics
-
Clozapine, olanzapine, quetiapine
Diabetes side effects of antipsychotics
-
Clozapine, olanzapine
Hyperlipidemia side effects of antipsychotics
-
Dry mouth, constipation, tachycardia, blurred vision, urinary retention
Anticholinergic
-
GABA depletion, changes in CNS permeability, disruption of da/ach, activation of latent seizure focus
Seizure side effects of antipsychotics
-
Anticholinergic, alpha-1 blockade, hyperprolactinemia, decreased testosterone
Genitourinary system: side effects of antipsychotics
-
Urinary retention/hesitancy. Erectile dysfunction. Decreased libido. Ejaculation dysfunction. Priapism
Genitourinary system: side effects of antipsychotics
-
Da blockade; anticholinergic blockade; inhibits sweating; concern with agents with greater anticholinergic properties, low potency typicals. Clozapine, olanzapine recommended. Mid potency typicals. Other atypicals
Thermoregulation: side effects of antipsychotics
-
Cataracts, retinopathy; photosensitivity, blue grey skin; phenothiazines; quetiapine
Ocular/dermatological: side effects antipsychotics
-
Typicals, risperidone. Most common with high potency typicals.
Hyperprolactinemia
-
Chlorpromazine, thioridazine
Hematological
-
Symptoms: amenorrhea, galactorrhea, gynecomastia
Hyperprolactinemia
-
Clozapine – reduces impulsive aggression. Self-harm/mutilation
Chronic aggression
-
Blockade of d2 receptors >> 5ht2a receptors
Typical antipsychotics
-
Blockade of d2 receptors >> 5ht2a receptors
Butyrophenone: haloperidol
-
Blockade of 5ht2a receptors > blockade of d2 receptors
Atypical antipsychotics
-
Mechanism of action uncertain. Suppresses inositol signaling and inhibits glycogen synthase kinase-3 (gsk-3), a multifunctional protein kinase
Lithium
-
Mechanism of action in bipolar disorder unclear
Anticonvulsants
-
Bind to specific GABAA receptors subunits at CNS neuronal synapses facilitating GABA –mediated chloride ion channel opening, enhance membrane hyperpolarization
Benzodiazepines
-
Mechanism uncertain: partial agonist at 5-ht receptors but affinity for d2 receptors also possible
5-ht-receptor agonist
-
Highly selective blockade of serotonin transporter (sert). Little effect on norepinephrine transporter (net)
Selective serotonin reuptake inhibitors (SSRIs)
-
Moderately selective blockade of net and sert
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
-
Mixed and variable blockade of net and sert
Tricyclic antidepressants (TCAs)
-
Inhibition of 5-ht2a receptor. Nefazodone also blocks sert weakly
5-ht2 antagonists
-
Increased norepinephrine and dopamine activity (bupropion). Net>sert inhibition (amoxapine, maprotiline). Increased release of norepi, 5-ht (mirtazapine)
Tetracyclic, unicyclic
-
Blockade of mao-a and mao-b (phenelzine, nonselective). Mao-b irreversible selective mao-b inhibition (lose dose selegiline).
Monoamine oxidase inhibitors (MAOIs)
-
The anticholinergic adverse effects of antidepressants are related to their interaction with
Muscarinic receptors
-
Blocking muscarinic receptors causes the classic anticholinergic symptoms
Constipation, dry mouth, blurred vision, drowsiness, urinary retention, etc.
-
A common adverse effect of atypical antipsychotics such as risperidone (Risperdal) and olanzapine (Zyprexa) is:
Weight gain
-
Chlorpromazine (Thorazine)
Tardive dyskinesia
-
It is important to monitor patients initiating therapy with clozapine (Clozaril) before treatment & weekly for the first 6 months because of the risk of:
Agranulocytosis
-
Enhances effects of gamma-aminobutyric acid
Alprazolam (Xanax)
-
Inhibits the reuptake of both serotonin (5-ht) and norepinephrine (ne)
Amitriptyline
-
Blocks use-dependent sodium channels and blocks the influx of calcium through the NMDA-glutamate receptor
Carbamazepine (Tegretol)
-
Potentiates the pharmacological effects of serotonin (5-ht) in the CNS
Escitalopram (Lexapro)
-
Potent serotonin 5-ht2-receptor and dopamine (d2)-receptor antagonist
Ziprasidone (Geodon)
-
Ad: bupropion (Budeprion xl)
Seizures
-
Ad: lamotrigine (Lamictal)
Rash
-
Ad: lithium
Nephrogenic diabetes insipidus
-
Ad: risperidone (Risperdal)
Pseudoparkinsonism
-
Ad: venlafaxine (Effexor)
Hypertension
-
Which receptor when stimulated produces antidepressant effects?
Atypical antipsychotics
-
Which SSRI causes the most anticholinergic adverse effects?
Paroxetine (Paxil)
-
Tardive dyskinesis
Typical antipsychotics
-
Psychiatric: schizophrenia (alleviate positive symptoms, bipolar disorder (manic phase)
Typical antipsychotics
-
Nonpsychiatric: antiemesis, preoperative sedation (promethazine), pruritus
Typical antipsychotics
-
Schizophrenia (alleviates (+) symptoms), bi-polar disorder (manic phase), Huntington’s chorea, Tourette’s syndrome
Butyrophenone: haloperidol
-
Schizophrenia – improve both (+) and (-). Bipolar disorder (olanzapine or risperidone adjunctive w/ lithium)
Atypical antipsychotics
-
Agitation ion Alzheimer’s and Parkinson’s (low doses)
Atypical antipsychotics
-
Major depression (aripiprazole)
Atypical antipsychotics
-
Bipolar affective disorder – prophylactic use can prevent mood swings b/w mania and depression
Lithium
-
Are also used both in acute mania and for prophylAXIS In depressive phase
Carbamazepine and lamotrigine
-
Is increasingly used as first choice in acute illness
Valproic acid
-
Acute anxiety states: panic attacks, generalized anxiety disorder, insomnia and other sleep disorders, relaxation of skeletal muscle, anesthesia (adjunctive) seizure disorders,
Benzodiazepines
-
Generalized anxiety states
5-ht-receptor agonist (buspirone)
-
Major depression, anxiety disorders, panic disorder, obsessive-compulsive disorder, PTSD, perimenopausal vasomotor symptoms, eating disorder (bulimia)
Selective serotonin reuptake inhibitors (SSRIs)
-
Major depression, chronic pain disorders, fibromyalgia, perimenopausal symptoms
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
-
Major depression, sedation and hypnosis (trazodone)
5-ht2 antagonists
-
Major depression not responsive to other drugs. Chronic pain disorders, incontinence, obsessive-compulsive disorder (clomipramine)
Tricyclic antidepressants (TCAs)
-
Major depression, smoking cessation (bupropion), sedation (mirtazapine), amoxapine and maprotiline rarely used
Tetracyclic, unicyclic
-
Major depression unresponsive to other drugs
Monoamine oxidase inhibitors (MAOIs)
-
Blockade of dopamine receptors may result in akathisia, dystonia, ¬parkinsonian symptoms, tardive dyskinesia, and hyperprolactinemia
Typical antipsychotics
-
Extrapyramidal dysfunction is major adverse effect
Butyrophenone: haloperidol
-
Agranulocytosis
Clozapine
-
Diabetes, hypercholesterolemia, wt. Gain
Clozapine, olanzapine
-
Hyper prolactinemia
Risperidone
-
Qt elongation
Ziprasidone
-
Renal elimination;
Lithium
-
Interactions: clearance decreased by thiazides and some NSAIDs
Lithium
-
Toxicity: tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias, pregnancy, category d
Lithium
-
Hematotoxicity and induction of p450 drug metabolism (carbamazepine). Rash (lamotrigine). Tremor. Liver dysfunction. Wt gain. Inhibition of drug metabolism (valproic acid)
Anticonvulsants
-
Toxicity: extensions of CNS depressant effects. Dependence liability. Interactions: additive CNS depression with ethanol and many other drugs.
Benzodiazepines
-
Tachycardia, paresthesias, GI distress. Interactions: cyp3a4 inducers and inhibitors
5-ht-receptor agonist
-
Well tolerated but cause sexual dysfunction. Interactions: some CYP inhibition
Selective serotonin reuptake inhibitors (SSRIs)
-
Anticholinergic, sedation, hypertension (venlafaxine), interactions: some cyp2d6 inhibition
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
-
Anticholinergic, α-blocking effects, sedation, weight gain, arrhythmias, seizure in overdose
Tricyclic antidepressants (TCAs)
-
Hypotension, insomnia
Monoamine oxidase inhibitors (MAOIs)
-
Interactions: hypertensive crisis with tyramine, other indirect sympathomimetics/serotonin syndrome with serotonergic agents, meperidine
Monoamine oxidase inhibitors (MAOIs)
-
SSRI moa
Selectively inhibit 5-ht reuptake by blocking 5-ht transporter
-
SSRI: most potent SSRIs re: blocking 5-ht transporter
Paroxetine & citalopram
-
SSRIs that produce effect on ne:
Fluoxetine and paroxetine (doses > 40mg)
-
SSRIs: advantages
Low affinity for histamine- 1, alpha-1, muscarinic (m) rec; so low sedation, no orthostasis, dry mouth or CV issues
-
SSRI w/longest half life
Fluoxetine
-
Most common AE reason for SSRI early dc
GI problems (titrate slowly, take w/meals)
-
Most common SSRI AE when starting drug
Akathisia (esp. w/fluoxetine)
-
Tx for SSRI akathisia
Start low, early am, benzo, trazo, and propranolol
-
Sexual dysfunction greatest/least with:
Greatest: paroxetine; least: citalopram
-
SSRI AE: sedation greatest with:
Paroxetine (d/t anticholinergic properties)
-
Serotonin syndrome s/s
Hyperreflexia, tremor, GI complaints, CV problems, seizures, respiratory depression, coma, death; concern re: SSRI combo w/other drugs
-
SSRI withdrawal s/s
Nightmares, flu-like symptoms, GI, shock-like sensations, & insomnia (seen usually in 2 to 7 days after abrupt d/c)
-
SSRI withdrawal worst with:
Paroxetine & sertraline (switch to fluoxetine?)
-
SSRI benefit seen in:
Atypical, psychotic, and dysthymia
-
Fluoxetine effective dose range
20-40 mg/day
-
Wt gain: SSRIs with greatest/least
Least: fluoxetine; greatest: paroxetine
-
Paroxetine effective dose range
30-50 mg/day
-
Citalopram/escitalopram effective dose range
20-60 mg/day
-
Lexapro effective dose range
10-20mg/day
-
Classes: equal in depression tx
SSRI, SNRI, atypicals
-
SNRI moa
Block reuptake of 5-ht and ne (& da)
-
SNRI moa: venlafaxine only produces effects on ne at:
A higher dose (so push dose pretty high)
-
SNRI moa: duloxetine has a high level of effect on:
Both 5-ht and ne
-
SNRI good to tx:
Refractory depression, melancholy; more physical pain sx of dependence; comorbid pain (duloxetine: dm peripheral neuropathy)
-
SNRI AE profile (which worse?)
Venlafaxine > duloxetine
-
SNRI side fx
GI (1st 3 wks); HTN (dose-dept (dbp) venlafaxine); withdrawal sim to SSRI
-
Use Venlafaxine IR cautiously in pts with:
HTN & cardiac dysfunction (use dulox or venla xr)
-
Mirtazapine (atypical) moa
Unique: blocks central alpha-2 recs increasing ne & 5-ht; antag 5-ht2, 5-ht3 post-synaptic recs
-
Mirtazapine AE
Somnolence, wt gain/inc appetite (used in cachectic pts), ortho hypotn
-
Bupropion moa
Weak reuptake inhibitor of ne and da
-
Bupropion active metabolite:
Hydroxy bupropion; has amphetamine properties (potent reuptake inhibitor of both ne and da)
-
Bupropion AE
Lower seizure threshold; vivid nightmares, delusions, psychosis
-
Do not give bupropion to pts with:
Eating disorders (low electrolytes): seizure risk
-
Bupropion dosing
Highest dose s/b usu 300; dose at early am and noon (d/t insomnia, etc)
-
Atypical: good option for pts with sedation / fatigue / sexual dysfunction
Bupropion
-
TCA moa
Block the reuptake of 5-ht and n; 1stgen: greater effect on 5-ht reuptake (doxepin); 2ndgen: greater effect on ne reuptake (esp. desipramine; clomipramine)
-
TCAs with best blockade of alpha- 1 & histamine- 1 recs:
Amitriptyline & doxepin
-
TCA AE
Anticholinergic (dry mouth, urine hesitancy, GERD; cardiovascular (ortho hypotn, tachy, conduction, HTN); CNS (tremor, sedation, myoclonic twitch); wt gain; sexual dysfunction
-
TCA dosing
Start at low dose, titrate slowly, switch to less offensive agent; bethanechol for anticholinergic AE; lethal in overdose
-
MAOI moa
Block destruction of monoamines by presynaptic neuronal mao; effect both central & peripheral; mao-a = on ne & 5-ht; mao-b = on phenylethylamine & da
-
Irreversible MAOI =
Phenelzine & tranylcypromine
-
MAOI AE
Wt gain; rash (selegiline); diet restriction (liver, cheese, wine, yeast)
-
Star-d general findings
6 wks necessary for pts achieve response; pts unable to tolerate med preferred switch; pts able to tolerate med preferred augmentation
-
Star-d: Buproprion XR:
Better results than buspirone
-
Star-d level 1
Start citalopram
-
Star-d level 2
Switch to: bupropion sr, CBT, sert, venlafaxine XR; or augment w/bupropion sr, BuSpar, CBT
-
Star-d level 2a
(if CBT in level 2): switch to: bupropion sr or venlafaxine XR
-
Star-d level 3
Switch to mirtazapine or nortriptyline; or augment w/lithium (poss t3 if bupropion, sertraline, venlafaxine)
-
Star-d level 4
Switch to tranylcypromine or mirtazapine combo w/venlafaxine xr
-
Bipolar: theories
Monoamine, dysregulation, anticholinergic, kindling, neuroendocrine, membrane & cation hypothesis, secondary messenger system, biologic rhythms, switch phenomenon
-
Lithium moa
Not well known; block da rec sensitivity; inc ne release in depn; dec ne release in mania; reduces beta-adrenergic stim of adenylate cyclase; inc 5-ht synth
-
Lithium indicated for
Acute mania; maintenance
-
Lithium advantages
Antidep & antimanic fx (no switching nec); prevent relapse; better than valproate at prevent suicide
-
Lithium: best results in pts:
Fewer prior episodes; hx euthymia; periods of good functioning; pos fh w/lithium
-
Lithium: reduced fx:
Severe mania w/psychotic; mixed episodes; rapid / continuous cycling; ETOH/ drug abuse
-
Lithium dosing
Start at 600-900; inc by 300 q 2-3d (target 900-2400)
-
Lithium monitoring
Draw trough 12h post last dose (tx day 5); then 1-2 wks for 1st months; 5 days post dose change
-
Lithium tx serum level
0.8 to 1.2 mEq/l (acute manic: poss 1.2 – 1.5); sr has no ref range
-
Lithium half life
Usu 24 h (8 – 20 h in mania)
-
Lithium AE (early)
Blocks ADH fx on its receptors (polydipsia / polyuria); mx weakness; fine hand (intentional) tremor
-
Lithium AE (late)
Ndi; increased lytes (na, k, h2o), cr; cardiac; persistent neuro probs (memory loss; mg, eps); thyroid; GI; inc WBC & wt
-
Leading cause of lithium noncompliance
Loss of creativity / memory
-
Lithium toxicity factors
Na restriction; dehydration; drug interactions
-
Lithium: mild toxicity =
1.5 – 2.0; prob memory/conc; GI; tremor
-
Lithium: moderate toxicity =
2.0-2.5; confusion, ataxia, nystagmus, inc DTR
-
Lithium: severe toxicity =
Over 3.0; choreoathetosis, seizure, coma, death
-
Tx lithium tox (>2.5)
- D/c lithium; gastric lavage; monitor levels
- Tx lithium tox (>3.5)
- D/c lithium; hemodialysis; monitor levels
- Lithium contraindications
- Renal disease; severe CV disease; hx leukemia; first tri of pg; hypersensitivity; breastfeeding?
-
Drugs that have anti-kindling properties
Anticonvulsants (valpro, carbamazepine, lamotrigine)
-
Bipolar drugs: category d (avoid in pg, dc in first trimester):
Lithium, valpro, carba
-
Valpro moa
Unk; prob inhib GABA metab &stim GABA synth
-
Valpro good for:
FDA: acute mania, rapid cycling (> lithium at mixed, secondary bipolar, subst induced)
-
Valpro less good for:
Depression
-
Valpro absorption delayed:
With food
-
Valpro AE
GI, sedation, ataxia/tremor, low PLT, liver probs
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Carbamazepine moa
Unk; prob block voltage-sensitive Na+ channels; block ca+ influx thru NMDA-glutamate receptor
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Carbamazepine efficacy
Xr same as lithium; also acute mania, prophylaxis, bipolar depn
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Carbamazepine better than lithium:
Severe mania; rapid cycling; mixed episodes
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Carbamazepine dosing
Start 200-400 mg/d; target 400-2400; max 15mg/kg/d
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Carbamazepine monitoring
No est tx level; anticonvulsant = 6-12 mcg/ml; carba levels 12h postdose & day 6
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Carbamazepine pk
Well absorbed (not affected by food); peak levels in 1-5 hr; 80% pro bound
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Carbamazepine AE
CNS tox; GI (divide doses); leukopenia, hepatotox, low PLT; SIADH, osteomalacia, derm
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Carbamazepine potentially lethal:
>15 mcg/ml
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Carbamazepine contraindications
Bone marrow depn; hypersensitivity
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Lamotrigine moa
Blocks voltage-sensitive Na+ and ca+ channels
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Lamotrigine efficacy
Maintenance (esp. bipolar depn); not for acute mania
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Lamotrigine pk
Well absorbed (not affected by food); peak levels 1-4 hr; half life 25 hr (so x1/d dose) (inc to 60 hr w/valpro)
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Lamotrigine AE
Usu well tolerated; Stevens Johnson’s syndrome; rash
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Antipsychotics dosing
Risperidone, olanzapine, quetiapine: mono or combo w/valp or lithium; aripiprazole, ziprasidone: monotx
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Antipsychotics good for:
Acute mania; mixed (quetiapine: bipolar depn)
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SSRIs in bipolar depn
Monotx inappropriate; high uncertainty in risk to manic switch
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Benzo: benefit in bipolar
Reduce insomnia and agitation in acute mania
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CCBs: benefit in bipolar
In lithium pts unable to tolerate AE
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Typical antipsychotics
Haloperidol (Haldol); fluphenazine (Prolixin); perphenazine (Trilafon); thioridazine (Mellaril); chlorpromazine (Thorazine
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Atypical antipsychotics
Clozapine (Clozaril); olanzapine (Zyprexa); risperidone (Risperdal); quetiapine (Seroquel); ziprasidone (Geodon); aripiprazole (Abilify)
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Choice of antipsychotic for: first episode
Atypicals
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Choice of antipsychotic for: noncompliance
Long-acting medications
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Choice of antipsychotic for: aggression
Clozapine; high potency typical; olanzapine and quetiapine
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Choice of antipsychotic for: insomnia
Olanzapine, quetiapine; low potency typicals
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Choice of antipsychotic for: dysphoria
Atypicals
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Choice of antipsychotic for: suicidal behavior
Atypicals
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Choice of antipsychotic for: substance abuse
Atypicals
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Choice of antipsychotic for: cognitive problems
Atypicals
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Choice of antipsychotic for: compulsive water drinking
Clozapine
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Sufficient trial w/typical / atypical antipsychotics =
4-6 weeks
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Antipsychotics: tx length: first episode
12 months following sx remission
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Antipsychotics: tx length: multiple episodes
5 yrs following sx remission
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Antipsychotics: relapse prevention
Slow taper (3-9 mo); 20% relapse rate after 1 yr of tx; 50% rate within 6 mo post-d/c of tx
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Antipsychotic tx resistance =
3 different antipsychotic meds from 2 different classes; hx of poor social functioning
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Only antipsychotic to show improvement in well defined treatment resistance:
Clozapine
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Monitoring for clozapine
Due to risk of low WBCs; monitor qwk for 6 mo, q2wks for 6 mo, q4wk for life; greatest risk first 6 mo
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Only true atypical antipsychotic:
Clozapine
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Akathisia is an AE of all antipsychotics except:
Clozapine
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Cardinal sx of pseudoparkinsonism
Akinesia, bradykinesia; pill rolling tremor; cogwheel rigidity; shuffling gait; masked facies
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Dystonia risk factors
Young males; high potency agents; high doses; previous dystonia
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Definition of dystonia
Mx spasms (jaw, tongue, neck)
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Definition of neuroleptic malignant syndrome (NMS)
Autonomic instability; mx rigidity; altered consciousness; high temp; myoglobinuria
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Definition of akathisia
Subjective restlessness; objective inability to be still
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Definition of tardive dyskinesia
Buccolingual movements (fly catchers tongue; puckering); facial movements (grimacing, chewing); truncal movements (rocking, gyrating); upper / lower extremities (irregular purposeless movements, foot tapping)
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Tx for tardive dyskinesia
Switch to atypical
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Treatment for akathisia
Start at low dose; decrease dose; switch to an atypical; anticholinergics are ineffective
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Main feature of atypicals is:
Diminished eps and prolactin levels
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Treatment for pseudoparkinsonism
Anticholinergics
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Risk factors for tardive dyskinesia
High doses; long length of tx; cumulative tx; increased age; organic mental disorder; dm; mood disorder; female
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Antipsychotic tx algorithm
Trial of SGA; trial of other SGA; [trial of single agent (FGA or new SGA) or clozapine]; clozapine plus (FGA, SGA, or ECT); trial of single agent (FGA or new SGA); combo tx
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Antipsychotic AE
#dystonia; akathisia; pseudoparkinsonism; tardive dyskinesia; NMS; CV (ortho hypotension, tachycardia, EKG: prolonged qt / torsades); wt gain; diabetes; hyperlipidemia; anticholinergic; sedation; seizure; gu; thermoregulation / fever; agranulocytosis
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Anti-anxiety med: adequate trial =
6-8 weeks
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Classes of anti-anxiety drugs
Benzodiazepines; SSRIs; SNRIs; buspirone; other (hydroxyzine, imipramine, and propranolol)
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Which drugs are first-line for anxiety?
Benzodiazepines; SSRIs; SNRIs
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Tx of choice for acute anxiety relief
Benzodiazepines
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Anxiety tx of choice for noncompliance / avoidance of withdrawal sx
Diazepam
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Advantage of buspirone
Lack of sedation AE; good if pt h/o substance abuse
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Advantage of beta blockers in anxiety tx
Good for pt w/ hx of CV sx; adjunct for refractory
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Moa: benzodiazepines
Potentiates inhibitory effect of GABA
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Moa: SSRIs
Selectively inhibit the reuptake of 5-ht by blocking the 5-ht transporter
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Moa: SNRIs
Block the reuptake of 5-ht and ne (and da)
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Moa: hydroxyzine
Potent antihistaminergic, anticholinergic, and antispasmodic effects
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Moa: imipramine (TCA)
Blocks reuptake of 5-ht and ne
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Moa: propranolol
Beta-blocker
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Bz side effects
CNS depression / sedation; anterograde amnesia; dependence / abuse
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Shorter acting benzodiazepines
Alprazolam; lorazepam; oxazepam
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Longer acting benzodiazepines
Chlordiazepoxide; clonazepam; diazepam
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Benzodiazepines: increased toxicity / mortality if:
Taken with other CNS depressants
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Benzodiazepine od mild sx
Drowsy, confusion, somnolence, impaired coordination, diminished reflexes, lethargy
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Benzodiazepine od serious sx
Ataxia, hypotonia, hypotension, hypnosis, coma, death
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Benzodiazepine od: tx:
Gastric lavage, supportive measures, flumazenil
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Benzodiazepine withdrawal sx
Anxiety, restlessness, insomnia, agitation, muscle tension, irritability
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Bz withdrawal sx more likely in:
Users of high doses for long periods of time
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Tx: by withdrawal
Taper over several weeks when discontinuing
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Antidepressants for anxiety dz:
SSRIs; venlafaxine; mirtazapine; TCA; MAOI
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SSRI dosing for anxiety
Delayed tx response; initiate w/smaller dose than ad dose
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Anxiety: MAOI reserved for:
Refractory cases
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FDA approved for panic disorder
Paroxetine, fluoxetine, sertraline, venlafaxine xr, alprazolam, clonazepam
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Tx for OCD
CBT first-line for mild; CBT and SSRI for severe (clomipramine if 2-3 failed SSRIs); tx mania, depression, or psychosis first
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