Psychotherapeutics: Schizophrenia

• This study guide covers psychotherapeutics, schizophrenia, bipolar disorder, depression, anxiety, ADHD, and insomnia.

Schizophrenia

• Schizophrenia may be caused by excessive dopamine receptor activation
• Schizophrenia may be caused by insufficient glutamate receptor activation
• Schizophrenia signs and symptoms are divided into positive, negative, and cognitive symptoms
• Conventional antipsychotics (FGA) and second-generation antipsychotics (SGA) are used to treat schizophrenia and are equally effective
• FGAs cause extrapyramidal symptoms and are cheaper
• SGAs have metabolic effects, risk for cardiovascular events, premature death, and are more expensive
• FGAs block dopamine receptors in the mesolimbic area of the brain and may also block ACh, histamine, and NE
• Positive symptoms of schizophrenia respond better to FGAs than negative symptoms
• Improvements are seen in 2-4 weeks, but treatment is not curative as it only provides symptomatic relief
• FGAs commonly cause extrapyramidal symptoms (EPS)
• Tardive dyskinesia (TD) is a notable adverse effect of FGAs
• Parkinsonism, acute dystonia, and akathisia, can be treated with anticholinergics, amantadine, or benzos/beta blockers
• Neuroleptic Malignant Syndrome (NMS) has a 5-20% mortality risk
• NMS is caused by antipsychotic medications and DA receptor antagonism, leading to rigidity, fever, sweating, and ANS instability
• Supportive measures and withdrawal of the antipsychotic medication can be used to treat NMS
• High potency FGA Haloperidol is preferred for initial use because it has early EPS symptoms, lower frequency of other AE
• Low potency FGA Chlorpromazine can cause sedation, orthostatic hypotension, anticholinergic side effects and photosensitivity reactions
• Second Generation Antipsychotics (SGAs) block dopamine and serotonin receptors and can block alpha1, histamine, and muscarinic receptors
• SGAs have lower EPS but higher metabolic effects such as diabetes, weight gain, and hyperlipidemia
• Agranulocytosis, seizures, myocarditis, EPS, and orthostatic hypotension are other AEs of SGAs
• All antipsychotics are equally effective and clozapine is more effective
• Treatment is individualized based on AE, cost, and dosing
• Nonadherence is a common cause of relapse, and pharmacologic therapy is continued indefinitely

Depression

• Women are more susceptible to depression than men
• Depression is the second most common mental health disorder
• Depression may be caused by the deficiency of NE and 5-HT
• Insomnia, anorexia, mental slowing, feelings of worthlessness, sleep disturbances, and suicidal ideation are symptoms of depression
• Serotonin and Norepinephrine Reuptake (SNRI's) side effects are similar to SSRI's, but SNRIs are less safe
• All antidepressant drug classes are equally effective but vary in AEs and drug interactions
• Antidepressants can increase Suicidal Ideation early in treatment

Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs block the reuptake of 5-HTs which results in higher Serotonin
• SSRIs have less adverse effects and are considered safer
• SSRIs typically cause weight gain and sexual dysfunction
• Nausea and agitation/insomnia are also adverse effects
• In late pregnancy, use of SSRIs can lead to withdrawal and pulmonary HTN in the newborn
• SSRIs have interactions with MAOIs, SNRIs, TCAs, analgesics, and triptans, increasing the risk of serotonin syndrome
• Increases the risk of bleeding with use of antiplatelets with anticoagulants

Tricyclic Antidepressants (TCAs)

• TCAs mechanism: 5-HT & NE reuptake inhibition
• TCAs are not very selective
• Orthostatic hypotension, anticholinergic effects, sedation, and cardiac toxicity are side effects of TCAs
• TCAs interact with MAOIs, sympathomimetics, and CNS depressants

Monoamine Oxidase Inhibitors (MAOIs)

• MAOIs inhibit MAO, reducing breakdown of NE, 5-HT, and DA and effects last x2 weeks
• MAOIs inhibit tyramine breakdown
• AEs incluse CNS stimulation, orthostatic hypotension, and many similar to SSRIs
• MAOIs has significant drug interactions due to tyramine and must avoid tyramine-containing foods
• Transdermal MAOIs (Selegiline) can lower HTN risk since bypassing the intestines/liver can reduce first-pass effect

Atypical Antidepressants

• Bupropion (DA/NE reuptake blocker) has minimal adverse effects, but can rarely cause agitation and seizures
• Mirtazapine (5-HT & NE increased release, H blocker) can cause somnolence/increased appetite/hyperlipidemia
• Esketamine is teratogenic and can cause dissociation and hypertension

Bipolar Disorder

• Bipolar disorder is characterized by disruptions in neuronal growth and recurrent mood fluctuations
• Bipolar disorder is treated with mood stabilizers with or without SGAs for acute mania
• Mood stabilizers are also used with or without SGAs +/- antidepressants for acute depression
• Long-term preventative treatment includes one or more mood stabilizers
• Lithium alters glutamate uptake/release and inhibits 5-HT antagonism and or glycogen synthase kinase-3 beta
• Lithium toxicity can occur and can cause polydipsia and hand tremors, and seizures

Insomnia

• Benzodiazepines, Benzodiazepine-like drugs, Melatonin agonists, Orexin antagonists, and Barbiturates are used to treat insomnia
• Benzodiazepines potentiate GABA and are generally well-tolerated and safe
• Benzodiazepine-like drugs agonize GABA receptors and are also generally well-tolerated and have a low risk of tolerance
• Ramelteon (melatonin agonist) can increase drug levels if used with depressants
• Melatonin regulates circadian rhythm and is safe
• Suvorexant (Orexin antagonist) promotes wakefulness
• Barbituates Agonize GABA receptors directly , and can lead to respiratory depression

Anxiety

• Anxiety is treated with nonpharmacologic interventions, SSRIs, SNRIs, buspirone, and benzodiazepines
• Buspirone has minimal adverse effects but must be taken with caution for patients with CYP450
• SSRIs, TCAs, benzodiazepines, propranolol, and psychotherapy are used to treat Anxiety Disorders

ADHD

• First-line drug for ADHD is CNS Stimulants, second-line is Nonstimulants
• CNS Stimulants methylxanthines, modafinil, and Amphetamines
• Amphetamines promote wakefulness
• Stimulants cause release of NE and DA and partially inhibit their reuptake
• Modafinil influences hypothalamic reuptake and well tolerated
• Modafinil is used for narcolepsy, shift work disorder, OSA/hypopnea syndrome, and fatigue
• Nonstimulants for ADHD include atomoxetine, clonidine, and guafacine, increase Alpha 2, and treat symptoms if ADHD