General Psychiatry PDF

General Psychiatry should not preclude antidepressant use in children, adolescents, and young adults because suicide is the second leading cause of death in this population. The results of three meta-analyses show that antidepressants decrease suicidal thoughts and acts in patients age 25–64 and de...

General Psychiatry should not preclude antidepressant use in children, adolescents, and young adults because suicide is the second leading cause of death in this population. The results of three meta-analyses show that antidepressants decrease suicidal thoughts and acts in patients age 25–64 and decrease suicidal acts in those older than 65. The number needed to treat for an SSRI in an adolescent with depression to prevent suicidal thoughts and acts is 4–10. M. Partial Response to Antidepressant Treatment 1. Ensure the patient is adherent and has received a therapeutic trial (as defined in section D2 earlier) of medication. 2. Patients can either be changed to a new antidepressant or receive adjunctive therapy. The 2016 Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines have a helpful algorithm and tables (see References section). 3. An antidepressant with a different mechanism of action can be added (e.g., bupropion or mirtazapine to an SSRI or SNRI). Data are not strong for this practice. Use caution when combining agents to avoid potential serotonin syndrome with at-risk agents. 4. SGAs may be used as adjuncts to antidepressant therapy. Almost all SGAs have been used, but only aripiprazole, brexpiprazole, and quetiapine ER have received FDA approval for this indication. Evidence also supports the use of risperidone. Olanzapine in combination with fluoxetine is also approved, but specifically for treatment-resistant depression. 5. Ketamine infusions are used off-label for depression and suicidality, particularly in patients who are not responsive or who are only partly responsive to antidepressants. 6. Other adjuncts include lithium, liothyronine, stimulants (including methylphenidate and modafinil), and buspirone. N. Treatment-Resistant Depression 1. Has many definitions; usually defined as inadequate response to at least two antidepressants 2. FDA-approved treatment options a. Olanzapine plus fluoxetine: Initial dosing is 6 mg/25 mg once daily; usual dosing is 6–18 mg/25–50 mg daily. b.  Esketamine (intranasal; Spravato) i. Approved for use in conjunction with an oral antidepressant ii. Also approved for major depression with suicidality iii. Mechanism of action: NMDA (N-methyl-d-aspartate) antagonist iv. Onset for treating depression symptoms is within hours. v. Dosing occurs in two phases: twice weekly during the induction phase, which lasts for 2 weeks, followed by the maintenance phase, in which dosing is weekly for 4 weeks and then every 1–2 weeks thereafter. vi. Carries black boxed warnings for sedation, dissociation, abuse and misuse (controlled substance, schedule III), and suicidal thoughts and behaviors vii. Common adverse reactions: Increased blood pressure, dissociative reactions including derealization and depersonalization, sedation, dizziness, anxiety, nausea, vomiting, and dysgeusia. Long-term use or misuse of ketamine has also been associated with ulcerative or interstitial cystitis. This has not been observed with esketamine in clinical trials but should be monitored. viii. Only available through a REMS program in which patients must be enrolled. Only approved pharmacies can dispense, and agent must be administered in a certified health care setting where patients are observed for at least 2 hours after administration. During this time, mental status and blood pressure must be monitored. Patients cannot drive until the following day. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-439 AL GRAWANY General Psychiatry III. BIPOLAR DISORDER A. Overview of Bipolar Disorder 1.  The DSM-5-TR defines bipolar disorder by the experience of a manic or hypomanic episode. Mania can be thought of as the affective opposite of depression. Consult the DSM-5-TR for a complete description of the diagnostic criteria. A manic episode is characterized by at least 1 week (or any duration, if hospitalization needed) of an abnormal and persistently elevated, expansive, or irritable mood accompanied by an abnormally and persistently increased goal-directed activity. The patient must also have three of the following symptoms (four if mood is irritable): inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, increased hyperactivity or psychomotor agitation, and involvement in high-risk activities without respect to the consequences. A hypomanic episode is a milder form of mania. This episode must exist for 4 days or longer and is not severe enough to warrant hospitalization, is not severe enough to cause marked social or occupational impairment, and is not associated with psychosis. 2. The DSM-5-TR includes two types of bipolar disorder (I and II): a. Bipolar I: Chronic disorder marked by one or more manic or mixed episodes. Although major depressive episodes are not necessary for the diagnosis, most patients have depressive episodes. b. Bipolar II: Chronic disorder marked by one or more major depressive episodes, accompanied by at least one hypomanic episode c. Cyclothymic disorder: Several periods of hypomania and mild depression, none of which meet the criteria for mania or major depressive episode d. Rapid cycling: At least four episodes of mania, hypomania, or depression in 1 year with 2 months between episodes or a switch to the opposite polarity 3. Bipolar disorder, particularly type II bipolar disorder, is often misdiagnosed as major depression. The diagnosis is important because the two conditions are treated differently. B. Lithium for Bipolar Disorders 1. The exact mechanism of action for lithium is unknown, but it appears to be neuroprotective. 2. Lithium continues to be the gold standard for treating type I bipolar disorder. Lithium is effective for the manic and depressive components. Although lithium is not a particularly good antidepressant as monotherapy in unipolar depression, it is effective in patients with bipolar disorder. Lithium has evidence for reducing suicidality when used for bipolar disorder. 3. Antimanic effects can occur in 1–2 weeks. Most clinicians use antipsychotics or benzodiazepines as adjunctive therapy during this period to cover the agitation and other symptoms. Antidepressant effects may take 6–8 weeks. 4. Pharmacokinetics: Lithium’s half-life is 20–24 hours. Lithium is excreted 95% unchanged by glomerular filtration, and anything that alters the glomerular filtration rate affects its clearance. Pharmacokinetic methods are available for early prediction of doses, but waiting 5–6 days for steady state seems to work just as well. 5. Initial dosing is 600–900 mg/day in divided doses, and dosing is then titrated according to response and tolerability. Maintenance doses are based on serum concentrations, symptom relief, and the occurrence of adverse effects. 6. A pre-lithium workup includes a complete blood cell count, electrolytes, renal function, thyroid function tests, urinalysis, ECG, and pregnancy test for women of childbearing age. 7. Monitoring: Serum concentrations must be monitored. Most clinicians will aim for concentrations of 0.8–1.2 mEq/L in acute mania and 0.6–1.0 mEq/L during maintenance. Concentration-response data are based on 12-hour postdose concentrations, so concentrations should be ordered in the morning 12 hours after the last evening dose. Renal function tests, thyroid function tests, and a urinalysis should be done every 6–12 months. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-441 General Psychiatry 8. Adverse effects are common with lithium, particularly during therapy initiation or after dose changes. Table 10 lists common adverse effects. 9. Symptoms of lithium toxicity include lethargy, coarse tremor, confusion, seizures, and coma and may even result in death. Patients who present to urgent care on lithium therapy should always be monitored for lithium toxicity before any medication adjustments. Lithium concentration and sodium/renal function should be obtained so that lithium concentrations can accurately be estimated. Treatment of choice for severe lithium toxicity is hemodialysis. Table 10. Adverse Effects Associated with Lithium Problem Rash or ↑ psoriasis Tremor CNS toxicity (e.g., agitation, confusion) GI (nausea, vomiting, diarrhea) Hypothyroidism Polydipsia or polyuria Interstitial fibrosis, glomerulosclerosis Teratogenicity Potential Interventions Discontinue the drug temporarily or permanently Reduce dose (Cp); add β-blocker Reduce dose (Cp) Reduce dose; try ER product, split doses Give levothyroxine; discontinue lithium, if necessary Reduce dose, manage fluid intake; single bedtime dosing helps Keep dose at lowest effective concentration; avoid dehydration Avoid during first trimester, if possible Cp = plasma concentration. 10. Pregnancy: Lithium passes the placental barrier and has been associated with cardiac and other abnormalities, including Ebstein abnormality when taken during the first trimester. However, it may have a lower risk than previously thought. Women of childbearing age should be counseled on its potential effects. Risks of discontinuing lithium therapy must be weighed against potential effects on the fetus when making decisions regarding lithium therapy during pregnancy. 11. Table 11 lists additional situations to consider during lithium therapy. Table 11. Situations to Consider During Lithium Therapy Situation Factors Drug interactions Diuretics Results Thiazides ↑ Li Cp; avoid use to reduce toxicity Furosemide ↑ Li Cp; avoid use to reduce toxicity Amiloride Little effect NSAIDs ↑ Li Cp; avoid use to reduce toxicity Theophylline ↓ Li Cp ACEIs ↑ Li Cp; avoid use to reduce toxicity Neuromuscular blockers Li prolongs action Neuroleptics Li may potentiate EPS Carbamazepine ↑ CNS toxicity Thyroid Li ↓ synthesis and release of thyroid hormone Hypothyroidism Pregnancy ↑ GFR ↓ Li Cp (first and second trimesters; third trimester may return to baseline) Aging ↓ GFR ↓ Li requirements ↑ Sensitivity to ADRs Li toxicity ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-442 General Psychiatry Table 11. Situations to Consider During Lithium Therapy (Cont’d) Situation Factors Results ↓ Renal function ↓ GFR, ↑ creatinine and BUN ↑ Li Cp Dehydration, salt restriction, and extrarenal salt loss ↑ Sodium reabsorption ↑ Li Cp ACEI = angiotensin-converting enzyme inhibitor; ADR = adverse drug reaction; BUN = blood urea nitrogen; Cp = plasma concentration; EPS = extrapyramidal symptoms; GFR = glomerular filtration rate; Li = lithium; NSAID = nonsteroidal anti-inflammatory drug. C. Antiseizure medications for Bipolar Disorder: These are also considered mood-stabilizing drugs that reduce manic and depressive episodes. See the Neurology chapter for additional drug-specific details. 1. Divalproex/valproic acid (Depakene, Depakote, Depacon, Stavzor): a. As effective as lithium in acute and prophylactic management. Divalproex appears to be good for bipolar disorder with rapid cycling but may not be as effective during depressive episodes. Divalproex is also beneficial for patients with dysphoric mania, mixed episodes, or a history of SUD. b. Black boxed warnings: i. Hepatotoxicity: Can result in death. Most common during the first 6 months of therapy. Risk is higher in children younger than 2 years. Liver function tests should be monitored routinely at the start of therapy and routinely thereafter, particularly during the first 6 months. ii. Mitochondrial disease: Patients with mutations of the mitochondrial DNA polymerase gamma (POLG) gene, such as Alpers-Huttenlocher syndrome, are at an increased risk of valproateinduced liver failure and death. Valproate is contraindicated in these patients. iii. Fetal risk: Valproate can cause major congenital malformations, particularly neural tube defects (including spina bifida), decreases in IQ scores, and neurodevelopmental disorders after in utero exposure. Valproate should not be used in women of childbearing age unless other medications have failed to provide adequate therapeutic benefit. Women of childbearing age who are taking valproate should also be receiving effective contraception. iv. Pancreatitis: Life-threatening pancreatitis can occur but is uncommon (less than 5%). Lifethreatening pancreatitis can recur with reinitiation of valproate, so valproate should not be reinitiated. c. Reference serum concentrations are 50–125 mcg/mL, but the exact concentration necessary for therapeutic effect is not well established. Serum concentrations should be interpreted in connection with clinical response. Therapeutic effects are usually seen with doses of 10–20 mg/kg/day. The trough serum concentration can be checked 3–5 days after initiation or a change in dose. Hypoalbuminemia increases the risk of increased free concentrations. Treatment nonresponse is common if the dose is too low; however, the free fraction increases as the serum concentration is increased (above 100–125 mcg/mL). Dose-related adverse effects that occur at serum concentrations greater than 80 mcg/mL include neurotoxicity, sedation, hair loss, and thrombocytopenia. The ER preparation has lower bioavailability than the enteric-coated preparation. The dose should be increased by 8%–20% when converting to the ER product. 2. Carbamazepine (Tegretol, Tegretol XR, Equetro): Effective for acute mania and maintenance therapy, particularly in patients with a history of head injury. Equetro is FDA approved for acute manic and mixed episodes. The serum concentration does not correlate well with therapeutic effect; however, it can be used to monitor for adherence and toxicity. Carbamazepine can also be added to lithium for patients who have not responded to monotherapy, but this increases the risk of neurotoxicity (see Lithium section earlier) and is not commonly done in practice. As a reminder, carbamazepine is a strong inducer of CYP metabolism. Carbamazepine also autoinduces its own metabolism and thus can take time to come to steady state. See the Neurology chapter for more information. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-443 General Psychiatry 3.  Lamotrigine (Lamictal): a. Has been approved for maintenance therapy. Lamotrigine appears particularly effective in preventing future depressive episodes of bipolar disorder. Lamotrigine is less effective than other mood stabilizers for preventing the manic phase. b. A Stevens-Johnson rash occurs in about 0.3% of adults and 1% of children. Lamotrigine must be discontinued if a rash occurs and should never be rechallenged. Risk increases with rapid dose titrations, high doses, young age, and concurrent use of valproic acid. The rash is most common within the first 2–8 weeks of therapy. If the medication is missed for greater than 3–5 half-lives (about 5 days), it must be retitrated from the starting dose. c. The dose titration must be halved if lamotrigine is given with valproate and doubled if given with carbamazepine because of drug-induced alterations in lamotrigine metabolism. The titration period is lengthy, so the onset of therapeutic effect can be delayed. For this reason, lamotrigine is not helpful in the acute setting. d. Lamotrigine has been associated with aseptic meningitis in adult and pediatric patients. Patients who experience headache, fever, chills, nausea, vomiting, stiff neck, rash, abnormal sensitivity to light, drowsiness, or confusion while taking lamotrigine should contact their health care professional right away. In 15 of 40 identified cases of aseptic meningitis, symptoms returned when patients were rechallenged with lamotrigine. Symptoms have occurred 1–42 days after the drug was started, and many patients required hospitalization. e. A rare but life-threatening immune reaction called hemophagocytic lymphohistiocytosis (HLH) can occur with lamotrigine. Onset is usually within the first few weeks of therapy. Symptoms may include fever, rash, hepatosplenomegaly, organ system dysfunction, and blood dyscrasias. Patients who develop this condition should be taken off lamotrigine and changed to alternative treatment. 4. Other antiseizure medications, including levetiracetam, oxcarbazepine, and topiramate, are used for bipolar disorder, but data regarding their efficacy are scarce. Data for gabapentin suggest it is ineffective. D. Antipsychotics for Bipolar Disorder: Antipsychotics, particularly SGAs, have mood-stabilizing properties. Antipsychotics can be used alone or with anticonvulsant mood stabilizers to treat bipolar symptoms. Metabolic adverse effects associated with antipsychotic use should be considered when medications are administered long term (see the Schizophrenia section). 1. Acute treatment: Antipsychotics treat acute symptoms of mania, including aggression and irritation, and any co-occurring psychosis. Antipsychotics are often combined with a traditional mood stabilizer for severe symptoms. All SGAs have received FDA approval for use in acute mania or mixed episodes except for brexpiprazole, clozapine, iloperidone, lumateperone, and lurasidone. For acute mania, the Canadian Network for Mood and Anxiety Treatments/International Society for Bipolar Disorders (CANMAT/ISBD) guidelines include aripiprazole, asenapine, cariprazine, paliperidone (more than 6 mg daily), quetiapine, and risperidone among the first-line agents. 2. Bipolar depression: Cariprazine, quetiapine, lumateperone, and lurasidone are approved for bipolar depression. Olanzapine is also approved for bipolar depression when combined with fluoxetine. Data for aripiprazole suggest it is ineffective for bipolar depression. 3. Maintenance treatment: The LAI antipsychotic formulations Risperdal Consta and Abilify Maintena have been approved for use in bipolar maintenance as monotherapy. The CANMAT/ISBD guidelines also recommend olanzapine and quetiapine. E. Dexmedetomidine for bipolar disorder: Similar to schizophrenia, dexmedetomidine can be used to treat acute agitation associated with bipolar disorder. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-444 General Psychiatry F. Benzodiazepines for Bipolar Disorder: Benzodiazepines are acutely helpful for agitation but not for the core symptoms, nor do they prevent relapses. Benzodiazepines are particularly useful for insomnia, hyperactivity, and agitation. Lorazepam or diazepam is often used in the acute setting. Long-term therapy is not recommended. G. Antidepressants for Bipolar Disorder: 1. Use of antidepressants in bipolar disorder is controversial, given concern for switching to the manic phase, particularly in patients with type I bipolar disorder. The risk appears greater with TCAs and SNRIs (particularly venlafaxine) than with SSRIs or bupropion. Because individual patients with bipolar disorder may benefit from antidepressants, the International Society for Bipolar Disorders (ISBD) stopped short of recommending against any use of antidepressants. However, antidepressants should not be used as monotherapy, and their use should be minimized in general. Antidepressants should not be used in bipolar depression if symptoms of mania are also present. The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trials found no statistically significant increased episodes of depression in patients taking mood stabilizers who discontinued their antidepressants. Patients with bipolar disorder taking mood stabilizers who received either paroxetine or bupropion were no more likely to achieve remission or have a durable recovery than those receiving placebo. These patients were also no more likely to switch to a manic phase. 2. Fluoxetine in combination with olanzapine is approved to treat depression associated with type I bipolar disorder. H. Type II Bipolar Disorder: The depressive phase tends to be more debilitating. Patients are usually functional during hypomanic episodes. Treatment therefore focuses on the depressive phase. Lithium is a first-line agent, but it may not achieve remission as monotherapy and takes time to relieve symptoms. Quetiapine is preferred for acute symptom treatment. Lurasidone can also be used. Lamotrigine is a reasonable alternative for longer-term symptom control, but because of its slow titration schedule, it is not useful in the acute setting. Other mood stabilizers can be used but may not be as efficacious as for type I bipolar disorder. Antidepressants are used more commonly but should be used with caution, and never as monotherapy. Olanzapine and fluoxetine may thus be an option. Patient Cases 13. A recent Iraq war veteran has responded to treatment with paroxetine for major depression for the past 3 weeks. Clinical presentation today includes experiencing nightmares, “feeling on edge all the time,” and having flashbacks of time in the war. After evaluation, the patient is diagnosed with posttraumatic stress disorder (PTSD). There is no history of substance dependence and no significant medical history. Which recommendation is most appropriate for this patient at this time? A. Continue paroxetine because it treats both PTSD and major depression. B. Discontinue paroxetine and initiate sertraline, which treats both PTSD and major depression. C. Continue paroxetine and add lorazepam for the anxiety symptoms. D. Discontinue paroxetine and initiate buspirone for the anxiety symptoms. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-445 General Psychiatry 5. Specific phobias are characterized by intense fear or anxiety induced by a specific object. 6. Obsessive-compulsive disorder (OCD), which used to be classified as an anxiety disorder, now has its own designation. Obsessions are recurrent and persistent thoughts, urges, or images that are intrusive and unwanted (e.g., fear of contamination, doubts, need for symmetry). Compulsions are ritualistic behaviors (e.g., washing the hands, combing the hair, cleaning the house) that relieve anxiety from the obsessions. 7. Posttraumatic stress disorder (PTSD), which also used to be classified as an anxiety disorder, has been moved to a category titled “Trauma- and Stressor-Related Disorders.” PTSD follows a traumatic event. PTSD is characterized by increased arousal and avoidance of stimuli that approximate the original traumatic event. 8. See the DSM-5-TR for more details on each specific disorder. B. Pharmacotherapeutic Options for Anxiety and Related Disorders 1. Benzodiazepines: These drugs have anxiolytic properties, and some have preventive efficacy for panic attacks. Benzodiazepines are not appropriate for all anxiety disorders (see the individual disorders for role). Depending on the agent, the onset can be quite rapid. The high-potency, short-half-life agents are the most rapid acting. They are effective for treating the acute somatic and autonomic symptoms of anxiety but do not adequately address the underlying cognitive and psychological pathology. a. Pharmacologically, benzodiazepines share, to various degrees, five properties: (1) anxiolytic, (2) hypnotic, (3) muscle relaxation, (4) anticonvulsant, and (5) amnesic actions. Tolerance of the anxiolytic action is uncommon. Benzodiazepines are differentiated by their half-life (plus or minus active metabolites) and potency. i. Table 12 compares the half-lives and equivalent doses of the five main/most commonly prescribed benzodiazepines for anxiety disorders. Table 12. Half-lives and Equivalent Doses of the Most Commonly Prescribed Benzodiazepines Agent Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Diazepam (Valium) Lorazepam (Ativan) a Half-Life (hr) 6–12 5–30a 20–50 20–100b 10–18 Equivalent Dose (mg) 0.5 25 0.5 10 1 Active metabolites: Desmethylchlordiazepoxide, demoxepam (half-life 14–95 hr), desmethyldiazepam (half-life 71–100 hr). Active metabolite: Desmethyldiazepam (half-life 71–100 hr). b b. Primary issues associated with benzodiazepines are tolerance and dependence. Tolerance of the hypnotic actions occurs within days. Dependence occurs within weeks to months of continued use. Abrupt cessation can lead to withdrawal and may be life threatening. Hence, it is generally recommended that treatment periods be restricted to 3–4 weeks, or about the time an antidepressant takes to begin to working for anxiety symptoms. After this time, the patient is tapered off the benzodiazepine to avoid withdrawal symptoms. If the patient has taken the benzodiazepine for a significant time, it can take several months to more than 1 year to complete. In practice, many patients go on to use benzodiazepines for long periods. Often, these patients are not in remission, despite treatment with maintenance medications. Minimize use of benzodiazepines in patients with a history of SUD or risk factors for SUD because of the risk of misuse. Information on benzodiazepine tapers can be found at deprescribing.org. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-447 General Psychiatry c. ​Risks associated with concomitant use with opioids: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients in whom alternative treatments are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. Both benzodiazepines and opioids carry a black boxed warning to this effect. 2. Antidepressants: SSRIs are also effective for several anxiety disorders and are the agents of choice for long-term treatment of anxiety disorders. Venlafaxine has been approved for GAD and social anxiety disorder. Duloxetine is also approved for GAD. Some initial symptoms may be improved within days, but the full benefit of treatment may take weeks, as for depression treatment. TCAs have preventive efficacy for panic disorder and anxiolytic activity. About 25% of patients with anxiety disorders (particularly GAD and panic disorder) have a hyper-stimulatory response to antidepressants, which can be confused with a worsening of the anxiety symptoms. This response is more common when therapy is first begun. Using low doses at first can help. Antidepressants can also help with anxiety that accompanies depression. Therapeutic doses are generally higher for almost all anxiety disorders (except social anxiety disorder) than for depression. 3. Buspirone: This drug has anxiolytic properties, but clinicians are divided on its real value in treating GAD. Buspirone has little efficacy for other anxiety disorders. The main drawback to buspirone is its long onset of action (weeks). In the meantime, the anxiety must be covered with another agent. Some clinicians use short-term benzodiazepines as a bridge until buspirone takes effect. Buspirone must also be dosed two or three times daily as scheduled, which decreases the chances for adherence. Buspirone should only be scheduled and never used as needed. 4.  Miscellaneous agents a. β-Blockers are sometimes used to block the peripheral symptoms of panic disorder or performance anxiety. b. MAOIs can be effective for panic disorder when the patient also has atypical depression. However, MAOIs are seldom used because of the potential for serious adverse effects. c. Antihistamines with sedating properties (e.g., hydroxyzine) can help reduce physical symptoms of anxiety. d. Barbiturates are seldom used. They are often less effective and can be lethal if taken in overdose. e. Antipsychotics are not considered first-line agents for anxiety disorders. Selected SGAs can be useful add-on therapy for OCD, GAD, and PTSD. 5. CBT should be an integral part of any therapeutic plan for anxiety disorders. C. Recommended Therapy for Specific Anxiety and Related Disorders 1. GAD a. Antidepressants: These are considered first-line agents. Evidence is strongest for the SSRIs (escitalopram, paroxetine [IR and CR], and sertraline) and the SNRIs (duloxetine and venlafaxine XR), all of which are FDA approved for the indication. b. Benzodiazepines: This class of drugs is rapidly effective; if possible, try to discontinue in 3–4 weeks or once the patient has remittance of symptoms. Benzodiazepines are more effective against somatic symptoms than against the underlying pathology. Evidence is strongest for alprazolam, diazepam, and lorazepam. c. Buspirone: Can be considered when benzodiazepines should be avoided (e.g., in patients with a history of SUD); takes 2–4 weeks to be effective. Buspirone is considered a second-line agent. d. Pregabalin: Depending on the guidelines, it is considered a first- or second-line agent (behind antidepressants). Does not carry an FDA indication for treating any form of anxiety. Limited data suggest similar efficacy with venlafaxine and benzodiazepines. Pregabalin can also be used as an adjunct. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-448 General Psychiatry e. Not effective: β-Blockers f. CBT or another type of psychotherapy should be included with pharmacotherapy. g. In treatment-refractory patients, augmentation with aripiprazole, quetiapine, olanzapine, or risperidone can be tried. 2. Panic disorder a. Antidepressants: First-line therapy. These include all the SSRIs and venlafaxine XR, all of which carry FDA approval. b. Benzodiazepines: High-potency agents; effective; rapid onset; evidence is strongest for alprazolam, clonazepam, diazepam, and lorazepam c. Not effective: Buspirone, β-blockers, antihistamines, trazodone. Bupropion is considered third line in some guidelines and is not recommended in others. d. CBT and other psychotherapies are effective. e. Patients with panic disorder tend to have a higher sensitivity to physical adverse effects. For this reason, these patients should be initiated on low doses of antidepressants – as low as 25 mg of sertraline or 10 mg of paroxetine. If the patient decides to stop antidepressant therapy, tapering should be very slow to minimize rebound panic symptoms. 3. OCD a. Serotonergic agents are effective – SSRIs (escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline). Depending on guidelines, clomipramine is considered a first- or second-line agent. Because of its adverse effect profile, clomipramine is typically used clinically as second line. Patients tend to require doses of antidepressants at the higher end of the dosing range. b. CBT is as effective as pharmacotherapy and is considered the treatment of choice for adolescents and adults with mild OCD. c. Alone, SSRIs often fail to control OCD completely. Not many other drugs help. Augmentation with haloperidol or an SGA (aripiprazole, olanzapine, quetiapine, or risperidone) may help. In general, high antipsychotic doses need to be used. 4. PTSD a. PTSD can be combat or non–combat related, and response to therapy may vary depending on the source of trauma. b. Psychotherapy is considered the cornerstone of treatment. Effective methods incorporate CBT, including exposure therapy and trauma-based cognitive processing therapy. c. Medications are considered adjuncts to psychotherapy. They are preferred if psychotherapists are not readily available or if a patient declines psychotherapy. d. SSRIs (sertraline and paroxetine are FDA approved, but evidence is also strong for fluoxetine) and venlafaxine XR are considered first-line agents. e. Augment with other agents to treat specific symptoms. i. Prazosin is commonly used for PTSD-associated nightmares, though evidence on its efficacy is conflicting. ii. Antiseizure medications can be used for aggression, anger, and depression (carbamazepine, lamotrigine, topiramate). Valproic acid is not considered effective. iii. SGAs can be used for psychotic symptoms (aripiprazole, quetiapine, risperidone). Some guidelines recommend against the use of olanzapine because of its high incidence of metabolic syndrome. f. Benzodiazepines are sometimes used acutely for sleep disturbances, but use should be very limited. Most data analyses indicate a lack of efficacy. Benzodiazepines have dissociative and disinhibiting properties and may worsen non-hyperarousal symptoms. Benzodiazepines may also interfere with the trauma recall (secondary to memory impairment) and fear-conditioning aspects of psychotherapy. The Veterans Affairs/Department of Defense (VA/DoD) guidelines recommend against the use of benzodiazepines. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-449