1 . The first American textbook on mental illness was published in
| A) | | 1812. |
| B) | | 1856. |
| C) | | 1901. |
| D) | | 1933. |
A BRIEF HISTORY OF PSYCHIATRY AND PSYCHOPHARMACOLOGY
In the United States, the first attempt at humane treatment of
psychiatric disorders was by the Quakers, who, in 1752, used the Pennsylvania Hospital in
Philadelphia to house patients in its basement; however, the environment in the hospital was
damaging to patients, some of whom were shackled to walls[1]. Other early institutions for people deemed "mentally disturbed" were
opened in the late 1700s in New York. In 1824, the Eastern Lunatic Asylum (now Eastern State
Hospital) opened in Lexington, Kentucky. By 1890, every state had at least one publicly
supported mental hospital, with populations that were rapidly expanding; by the 1950s, these
institutions housed more than 500,000 patients [1]. One of the earliest practitioners of what could be called psychiatry was
Dr. Benjamin Rush, who has been called the father of American psychiatry and who wrote the
first American textbook on mental diseases (Medical Inquiries and
Observations upon Diseases of the Mind) in 1812.
2 . In the mid-1900s, what approach to mental health treatment was overwhelmingly popular?
| A) | | Art therapy |
| B) | | Psychoanalysis |
| C) | | Pharmacotherapy |
| D) | | Electroconvulsive therapy (ECT) |
A BRIEF HISTORY OF PSYCHIATRY AND PSYCHOPHARMACOLOGY
By the mid-20th century, psychoanalysis became overwhelmingly popular and was employed not only in the treatment of patients with anxiety or neurosis but also in the treatment of patients with more severe psychiatric disorders, such as psychosis, for which talk therapy had little to offer. Some postulate that the development of psychoanalysis stunted the development of psychopharmacology by promoting the notion that talk therapy could effectively treat all mental health issues.
3 . Most experts date the birth of modern psychopharmacology to the synthesis of
| A) | | lithium. |
| B) | | fluoxetine. |
| C) | | alprazolam. |
| D) | | chlorpromazine. |
A BRIEF HISTORY OF PSYCHIATRY AND PSYCHOPHARMACOLOGY
The term psychopharmacology traces its roots to 1920, appearing first in the title of a paper by David Macht describing the use of quinine and antipyretics in tests on neuromuscular coordination. However, most experts date the true birth of psychopharmacology to 1951, when chlorpromazine was first synthesized [5].
4 . Which of the following agents is the most widely prescribed high-potency typical antipsychotic?
| A) | | Loxapine |
| B) | | Haloperidol |
| C) | | Chlorpromazine |
| D) | | Methotrimeprazine |
ANTIPSYCHOTIC MEDICATIONS
Typical antipsychotics (Table 1) have a primary site of action at the D2 receptor and are potent D2 receptor blockers. They also have noradrenergic, cholinergic, and histaminergic blocking action. These agents can also be described as high, intermediate, or low potency. High-potency antipsychotics are prescribed in lower doses, with the most widely prescribed of these being haloperidol (Haldol). Haloperidol is available in oral, intramuscular (IM), and long-acting IM decanoate formulations. Low-potency antipsychotics are prescribed in higher doses; the most widely used of these is chlorpromazine [17,18].
5 . Which of the following typical antipsychotics may be administered via inhalation?
| A) | | Loxapine |
| B) | | Flupentixol |
| C) | | Thioridazine |
| D) | | Zuclopenthixol |
ANTIPSYCHOTIC MEDICATIONS
TYPICAL ANTIPSYCHOTIC MEDICATIONS
| Drug | Dose Range | Typical Starting Dose | Usual Maintenance Dosea | Route(s) | Indication(s) |
|---|
| Chlorpromazine | 25–800 mg/day | 25–50 mg/day | 100–400 mg daily or BID | IM, IV, PO | Schizophrenia, bipolar disorder, intractable hiccups, agitation/aggression
(severe, acute) associated with psychiatric disorders |
| Droperidol | 0.625–10 mg/day | 2.5–10 mg/day | 10 mg/day | IM, IV | Postoperative nausea/vomiting, acute undifferentiated agitation
(off-label) |
| Flupentixol |
| IM:5–40 mg/day | | Oral:1–6 mg/day |
|
| IM:5–20 mg/day | | Oral: 1 mg/day |
|
| IM: 20–40 mg every 2 to 3 weeks | | Oral: 3–6 mg/day in divided doses |
| Oral, IM (depot) | Schizophrenia |
| Fluphenazine | 2.5–40 mg/day | 2.5–10 mg every 6 to 8 hours |
| Oral: 5–40 mg/day | | IM: 12.5–25 mg every 2 to 4 weeks |
| PO, IM, decanoate | Psychotic disorders |
| Haloperidol (Haldol) | 0.5–30 mg/day | Oral: 0.5–5 mg BID | 5–15 mg BID | PO, IM, IV, decanoate | Bipolar disorder, hyperactive delirium, schizophrenia, Tourette-associated
tics, acute/severe agitation (off-label) |
| Loxapine (Adasuve) | 5–125 mg BID | 10–25 mg BID | 60–100 mg BID | PO, inhalation | Schizophrenia, acute agitation |
| Methotrimeprazine | 6–200 mg/day |
| Mild: 6–25 mg/day in divided doses | | Severe: 50–75 mg/day in divided doses |
|
| Oral: Up to 1 g/day in divided doses | | IM: 75–100 mg/day in divided doses |
| PO, IM | Anxiety/tension disorders, insomnia, nausea/vomiting, pain, psychotic
disorders |
| Molindone | 5–75 mg TID | 5–15 mg BID | 10–25 mg TID | PO | Schizophrenia |
| Periciazine | 5–40 mg/day | 5–20 mg in the morning, followed by 10–40 mg in the evening | Titrate to lowest effective dose | PO | Psychosis |
| Perphenazine | 2–24 mg BID | 2–4 mg BID | 8–24 mg BID | PO | Schizophrenia, nausea/vomiting |
| Pimozide | 0.5–10 mg/day | 1–2 mg/day in divided doses | Lowest effective dose (maximum: 10 mg) | PO | Tourette syndrome, delusional infestation (off-label) |
| Prochlorperazine (Compro) | 2.5–25 mg/day |
| Oral: 5–10 mg every 6 to 8 hours | | IM: 5–10 mg every 3 to 4 hours | | IV: 2.5–10 mg every 3 to 4 hours | | Rectal: 25 mg every 12 hours |
| Maximum: 40 mg/day | PO, IM, IV, rectal | Acute nausea and vomiting |
| Thioridazine | 50–800 mg/day | 50–100 mg TID | 200–800 mg BID or QID | PO | Schizophrenia |
| Thiothixene | 2–30 mg BID | 2–5 mg BID | 10–15 mg BID | PO | Schizophrenia |
| Trifluoperazine | 2–40 mg/day | 1–2 mg BID | 15–20 mg/day | PO | Schizophrenia |
| Zuclopenthixol | 10–400 mg/day |
| Oral: 10–50 mg/day in divided doses | | IM: 50–150 mg/day |
|
| Oral: 20–40 mg/day | | IM: Up to a maximum 400 mg/day |
| PO, IM | Schizophrenia, psychoses (acute and long-term) |
| aAll dosing is for adults. For pediatric uses,
consult pediatric-specific literature. | | BID = twice daily, IM = intramuscular, IV = intravenous, PO = oral, QID =
four times per day, TID = three times per day. |
|
6 . Patients who are prescribed typical antipsychotics should be monitored for neurologic side effects using the standardized
| A) | | Aldrete score. |
| B) | | brain imaging. |
| C) | | Mini-Mental State Exam. |
| D) | | Abnormal Involuntary Movement Scale (AIMS). |
ANTIPSYCHOTIC MEDICATIONS
Patients who are prescribed typical antipsychotics should be monitored for neurologic side effects using the standardized Abnormal Involuntary Movement Scale (AIMS) (Figure 1). The AIMS consists of 12 items and can usually be completed within 10 minutes. It was developed specifically to detect and record the occurrence of tardive dyskinesia in any patient taking neuroleptic medication. Tardive dyskinesia is a syndrome characterized by abnormal involuntary movements of the patient's face, mouth, trunk, or limbs, and it affects 20% to 30% of patients who have been treated for months or years with neuroleptic medications. Patients who are older, are heavy smokers, or have diabetes are at increased risk of developing tardive dyskinesia. For most patients, this side effect develops three months after the initiation of neuroleptic therapy; in elderly patients, however, tardive dyskinesia can develop after as little as one month [20].
7 . Antagonism of what neurotransmitter receptor is most correlated with weight gain and adverse metabolic effects associated with antipsychotics?
| A) | | Histamine (H1) |
| B) | | Dopamine (D2) |
| C) | | Serotonin (5HT) |
| D) | | Norepinephrine |
ANTIPSYCHOTIC MEDICATIONS
Meta-analyses have shown that all antipsychotics are associated with an increased risk for weight gain, with the greatest gain seen with atypical agents (clozapine and olanzapine) and the least with typical agents (haloperidol). Numerous studies have concluded that H1 receptor antagonism action is most correlated with weight gain, although other receptor sites (including 5HT receptors) were also significantly associated with weight gain [21].
8 . Which of the following medications is approved for the management of Parkinson-associated psychosis?
| A) | | Clozapine |
| B) | | Aripirazole |
| C) | | Risperidone |
| D) | | Pimavanserin |
ANTIPSYCHOTIC MEDICATIONS
ATYPICAL ANTIPSYCHOTIC MEDICATIONS
| Drug | Dose Range | Typical Starting Dose | Usual Maintenance Dosea | Route(s) | Indication(s) |
|---|
| Aripiprazole (Abilify) | 2–30 mg/day | 2.5–5 mg/day | 10–20 mg/day | PO, decanoate | Bipolar disorder, treatment-resistant depression (adjunctive),
schizophrenia |
| Asenapine (Saphris, Secuado) | 5–10 mg BID | 5 mg BID | 10 mg BID | SL, transdermal patch | Bipolar disorder, schizophrenia |
| Brexpiprazole (Rexulti) | 2–4 mg/day | 1 mg/day | 4 mg/day (with titration) | PO | Schizophrenia, treatment-resistant depression (adjunctive) |
| Cariprazine (Vraylar) | 1.5–6 mg/day | 1.5–6 mg/day | 3–6 mg/day (with titration) | PO | Bipolar disorder, schizophrenia |
| Clozapine (Clozaril, Versacloz) | 25–800 mg/day | 25–800 mg/day | 250–400 mg hourly or BID (Strict titration guidelines, must be in REMS) | PO (including oral disintegrating tablet) | Schizophrenia, suicidal behavior in schizophrenia or schizoaffective
disorder |
| Iloperidone (Fanapt) | 1–12 mg/day | 1–2 mg BID | 12 mg/day (lower doses in patients with hepatic dysfunction) | PO | Schizophrenia |
| Lumateperone (Caplyta) | 42 mg/day | 42 mg/day | 42 mg/day | PO | Schizophrenia |
| Lurasidone (Latuda) | 20–80 mg/day | 20 mg/day | 80 mg/day | PO | Bipolar major depression, schizophrenia |
| Olanzapine (Zyprexa) | 2.5–20 mg/day | 2.5–5 mg/day | 15–20 mg/day | PO, IM, IV | Bipolar disorder, agitation/aggression associated with psychiatric disorders,
schizophrenia |
| Paliperidone (Invega) | 3–12 mg/day | 3 mg/day | 6 mg/day | PO, IM decanoate | Schizophrenia, schizoaffective disorder |
| Pimavanserin (Nuplazid) | 34 mg/day | 34 mg/day | 34 mg/day | PO | Parkinson-associated psychosis |
| Quetiapine (Seroquel) | 25–800 mg/day | 50 mg/day | 200–400 mg/day | PO, extended-release | Bipolar disorder, schizophrenia |
| Risperidone (Perseris, Risperdal) | 0.5–6 mg/day | 1–2 mg/day | 4 mg/day | PO, IM decanoate | Bipolar disorder, schizophrenia |
| Ziprasidone (Geodon) | 20–80 mg/day | 40 mg BID | 80 mg BID | PO, short-acting IM | Bipolar disorder (adjunctive), schizophrenia |
| aAll dosing is for adults. For pediatric uses,
consult pediatric-specific literature. | | BID = twice daily, IM = intramuscular, IV = intravenous, PO = oral, QID =
four times per day, REMS = Risk Evaluation and Mitigation Strategy, SL =
sublingual. |
|
9 . What is the only atypical antipsychotic available in a sublingual formulation?
| A) | | Asenapine |
| B) | | Quetiapine |
| C) | | Iloperidone |
| D) | | Brexiprazole |
ANTIPSYCHOTIC MEDICATIONS
Asenapine is a dibenzo-oxepino pyrrole atypical antipsychotic with mixed serotonin-dopamine antagonist activity. It is unique as the only atypical antipsychotic available in a sublingual formulation. When administered sublingually for the management of agitation, the onset of effects is seen within 15 minutes. In bipolar disorder/acute mania, initial effects are present within days, with continued improvements over one to two weeks [19]. In patients being treated for schizophrenia, the initial effects are observed within one to two weeks, and maximal effects are noted in four to six weeks.
10 . At the initiation of clozapine therapy, absolute neutrophil count (ANC) monitoring should be conducted
| A) | | weekly for six months. |
| B) | | every two weeks for 6 to 12 months |
| C) | | monthly for six months. |
| D) | | every six months. |
ANTIPSYCHOTIC MEDICATIONS
The Clozapine REMS Program provides a centralized point of access for prescribers and pharmacies to certify before prescribing or dispensing clozapine and to enroll and manage patients on clozapine treatment [23]. The monitoring requirements are established for the general population (most patients being prescribed clozapine) and for patients with benign ethnic neutropenia (BEN). BEN is a condition observed in certain ethnic groups whose average ANCs are lower than "standard" laboratory ranges for neutrophils. It is most commonly observed in individuals of African descent (approximate prevalence of 25% to 50%), some Middle Eastern ethnic groups, and in other non-White ethnic groups with darker skin; it is also more common in men [23]. At initiation of therapy, ANC monitoring should be conducted weekly for six months. If ANC levels remain ≥1,500/mcL in the general population or ≥1,000/mcL in patients with BEN, monitoring frequency may be reduced to every two weeks from 6 to 12 months, then monthly after 12 months. If neutropenia develops, monitoring may be more frequent, from three times weekly to daily depending on the severity of the neutropenia [23]. Prescribers are required to submit patients' ANC levels to the Clozapine REMS Program for every prescription of clozapine according to the patient's monitoring frequency.
11 . All of the following are common adverse effects of quetiapine, EXCEPT:
| A) | | Bradycardia |
| B) | | Dyslipidemias |
| C) | | Extrapyramidal reaction |
| D) | | Orthostatic hypotension (particularly among elderly patients) |
ANTIPSYCHOTIC MEDICATIONS
There are no absolute contraindications to the use of quetiapine, aside from hypersensitivity. Drowsiness is a common effect and may be severe enough to result in impairment, inability to safely carry out activities of daily living (increased fall risk), and nonadherence [19]. Other common adverse effects include hypertension, orthostatic hypotension (particularly among elderly patients), tachycardia, dyslipidemias, weight gain, increased appetite, xerostomia, agitation, dizziness, extrapyramidal reaction, headache, and withdrawal syndrome.
12 . When risperidone is given by orally disintegrating tablet to manage acute agitation, the meant time to calm is
| A) | | 5 minutes. |
| B) | | 30 minutes. |
| C) | | 70 minutes. |
| D) | | 90 minutes. |
ANTIPSYCHOTIC MEDICATIONS
Risperidone's high 5-HT2 and dopamine-D2 receptor antagonist activity is responsible for its antipsychotic action. However, alpha1, alpha2 adrenergic, and histaminergic receptors are also antagonized with high affinity. Onset of action is within days to 2 weeks, though peak effect may be experienced after up to 12 weeks [19]. An orally disintegrating tablet may be used to manage acute agitation, with 70 minutes mean time to calm.
13 . In patients taking antipsychotic medications, the onset of neuroleptic malignant syndrome symptoms is generally apparent within
| A) | | one day of treatment initiation. |
| B) | | two weeks of treatment initiation. |
| C) | | two months of treatment initiation. |
| D) | | six months of treatment initiation. |
ANTIPSYCHOTIC MEDICATIONS
Onset of symptoms is generally apparent within two weeks of treatment initiation. Clinical presentation consists of rigidity/stiffness, high fever, sweating, confusion, unstable blood pressure, and agitation. Signs and symptoms usually progress to a peak after three days. Prompt recognition is necessary to avoid significant morbidity and mortality, and treatment is immediate cessation of the antipsychotic medication and implementation of supportive measures (e.g., hydration, cooling) [30]. In more severe cases, administration of bromocriptine mesylate or dantrolene sodium may be indicated.
14 . Which of the following statements regarding the treatment of tardive dyskinesia is TRUE?
| A) | | There are no medications approved for the treatment of tardive dyskinesia. |
| B) | | If a new medication will be used, haloperidol should be considered first, as it has the lowest risk of tardive dyskinesia. |
| C) | | Patients should be informed that tardive dyskinesia symptoms will improve immediately as medication dosages are lowered. |
| D) | | The primary consideration for patients receiving typical antipsychotics should be dose reduction or switching medications. |
ANTIPSYCHOTIC MEDICATIONS
Treatment of tardive dyskinesia can be difficult and an impediment to the clinical stabilization of the patient. The primary consideration for patients receiving typical antipsychotics should be dose reduction or switching medications. Patients should be warned that tardive dyskinesia symptoms may initially worsen transiently as medication dosages are lowered (i.e., withdrawal-emergent dyskinesias). If a new medication will be used, clozapine should be considered first, as it has the lowest risk of tardive dyskinesia. However, it is vital to ensure that control of psychosis is maintained, particularly in patients at risk for self-harm or violence.
In 2017, the FDA approved the first medications for the treatment of tardive dyskinesia: valbenazine (Ingrezza) and deutetrabenazine (Austedo). The initial dose of valbenazine is 40 mg once daily. This is increased to 80 mg once daily after one week [19]. Continuation of a daily dose of 40 mg or 60 mg may be considered based on response and tolerability. Improvement is seen in 2 to 6 weeks, with the result stabilizing between 16 to 32 weeks. Deutetrabenazine is started at a dosage of 6 mg twice daily. This is increased as needed and tolerated in increments of 6 mg/day up to a maximum of 48 mg/day [19].
15 . What is the typical starting dose of fluoxetine?
| A) | | 1.5 mg/day |
| B) | | 20 mg/day |
| C) | | 75 mg/day |
| D) | | 200 mg/day |
ANTIDEPRESSANT MEDICATIONS
ANTIDEPRESSANT MEDICATIONSa
| Drug | Dose Range | Typical Starting Dose | Potential Adverse Effects | Comments |
|---|
| MAOIs |
| Selegiline (Emsam, Zelapar) | 6–12 mg transdermal patch every 24 hours | 6 mg transdermal patch every 24 hours |
| Serious food and drug interactions | |
| Also used in treatment of Parkinson disease |
| Isocarboxazid (Marplan) | 10–40 mg/day | 10 mg BID | May take 3 to 6 weeks to see effects. Dose should be reduced once maximum
clinical effect is seen. If no response obtained within 6 weeks, additional titration
is unlikely to be beneficial. |
| Phenelzine (Nardil) | 15–30 mg every 8 hours | 15 mg every 8 hours | — |
| Tranylcypromine (Parnate) | 10–60 mg BID | 10–30 mg BID | — |
| Moclobemide | 300–600 mg/day | 300 mg/day in 2 divided doses | — |
| Tricyclic Antidepressants |
| Amitriptyline | 50–300 mg/day | 25–50 mg/day as a single dose at bedtime or in divided doses | Xerostomia, sedation | Follow levels and EKG/QTc |
| Clomipramine (Anafranil) | 12.5–250 mg at night | 12.5–50 mg at night | Approved for OCD, off-label for MDD |
| Doxepin (Silenor) | 25–300 mg at night or in divided doses | 25–50 mg at night | Usually reserved for treatment-resistant MDD |
| Imipramine | 25–300 mg at night or in divided doses | 25–50 mg at night or in divided doses | — |
| Trimipramine | 25–300 mg at night or in divided doses | 25–50 mg at night or in divided doses | — |
| Amoxapine | 25–600 mg total (may be BID dosing) | 25–50 mg at bedtime or BID | The maximum dose in outpatients is 400 mg/day; in hospitalized patients, it is
600 mg/day. |
| Desipramine (Norpramin) | 25–300 mg daily or in divided doses | 25–50 mg/day | — |
| Nortriptyline (Pamelor) | 25–150 mg/day | 25 mg at night | — |
| Protriptyline | 10–60 mg daily divided in 3 to 4 doses | 10–20 mg daily divided in 3 to 4 doses | — |
| SSRIs |
| Citalopram (Celexa) | 20–40 mg/day | 20 mg/day | GI upset |
| Few drug interactions | | Lower maximum daily dose (20 mg) recommended for patients at risk for QTc
prolongation |
|
| Escitalopram (Lexapro) | 10–20 mg/day | 10 mg/day | GI upset | Also approved for generalized anxiety disorder |
| Fluoxetine (Prozac) | 20–80 mg/day | 20 mg/day | GI upset, activation syndrome | Also approved for bulimia, panic disorder, generalized anxiety disorder, OCD, and
PMDD |
| Fluvoxamine, immediate-release | 50–300 mg at night | 50 mg at night | Nausea | Approved for OCD, off-label for MDD |
| Fluvoxamine, controlled-release | 100–300 mg at night | 100 mg at night |
| Paroxetine (Brisdelle, Paxil, Pexeva) | 20–50 mg/day | 20 mg/day | Sedation | Also approved for generalized anxiety disorder, panic disorder, OCD,
PTSD, PMDD, social anxiety disorder, and vasomotor symptoms of menopause |
| Paroxetine, controlled-release (Paxil CR) | 25–62.5 mg/day | 25 mg/day | Sedation |
| Sertraline (Zoloft) | 50–200 mg/day | 50 mg/day | GI upset | Also approved for OCD, panic disorder, PMDD, PTSD, and social anxiety
disorder |
| SNRIs |
| Venlafaxine (Effexor) | 37.5–375 mg BID | 37.5–75 mg BID | Nausea, hypertension, xerostomia, drowsiness | Use with caution in patients with glaucoma |
| Venlafaxine, extended-release (Effexor XR) | 37.5–225 mg/day | 37.5–75 mg/day | Nausea, xerostomia, hypertension |
| Use with caution in patients with glaucoma | | Also approved for generalized anxiety disorder, panic disorder, and social
anxiety disorder |
|
| Levomilnacipran (Fetzima) | 20–120 mg/day | 20 mg/day | Orthostatic hypotension (dose related), nausea | — |
| Desvenlafaxine (Pristiq) | 50–100 mg/day | 25-50 mg/day | Dizziness, insomnia, hyperhidrosis, nausea, xerostomia, anxiety |
| No evidence that dosing over 50 mg is more effective | | In patients who are sensitive to side effects (particularly anxiety),
consider lower starting dose (25 mg/day) |
|
| Duloxetine (Cymbalta, Drizalma Sprinkle) | 40–120 mg/day | 40–60 mg/day | Activation syndrome, weight loss, GI upset, headache |
| Also approved for fibromyalgia, generalized anxiety disorder, chronic
musculoskeletal pain, and diabetic neuropathic pain | | Avoid in patients with renal impairment (CrCl <30 mL/min) |
|
| Milnacipran (Savella) | 25–100 mg BID | 25–50 mg BID | Nausea, headache, constipation, insomnia | Approved for fibromyalgia, off-label for MDD |
| Atypical Antidepressants |
| Bupropion (Aplenzin) | 75–450 mg/day in divided doses | 100 mg BID | Increased seizure threshold, weight loss, GI upset,
agitation |
| Also approved for smoking cessation and seasonal affective disorder | | No sexual side effects |
|
| Bupropion, sustained-release (Wellbutrin SR) | 150–200 mg BID | 150 mg/day in the morning |
| Bupropion, extended-release (Forfivo XL, Wellbutrin XL) | 150–450 mg/day in the morning | 150–175 mg/day in the morning |
| Mirtazapine (Remeron) | 15–45 mg at bedtime | 15 mg at bedtime | Weight gain, increased appetite, drowsiness | Weight gain may limit satisfaction and compliance |
| Trazodone | 50–600 mg BID | 50 mg BID | Drowsiness, dizziness, xerostomia, GI upset | — |
| Nefazodone | 50–600 mg in divided doses | 50–100 mg BID | Headache, xerostomia, drowsiness | Should not be initiated in individuals with active liver disease or elevated
baseline serum transaminases |
| Brexanolone (Zulresso) | — |
| 60-hour continuous IV infusion | | (Total dose: 270 mg/kg) |
| Drowsiness, sedation, xerostomia, dizziness |
| Used only for inpatient treatment of postpartum depression | | Requires REMS |
|
| Esketamine (Spravato) | 56–84 mg intranasal twice weekly | 56–84 mg intranasal twice weekly | Dissociation, anxiety, nausea, dizziness |
| Reserved for treatment-resistant MDD or MDD with suicidality | | Requires REMS |
|
| Serotonin 5-HT1A Receptor Agonist |
| Gepirone (Exxua) | 18.2–72.6 mg | 18.2 mg/day | Nausea, dizziness | No sexual side effects or weight gain |
| Multimodal Agents |
| Vilazodone (Viibryd) | 10–40 mg/day | 10 mg/day | Headache, GI upset | Alternative agent |
| Vortioxetine (Trintellix) | 5–20 mg/day | 5–10 mg/day | Nausea, sexual dysfunction |
| aAll information provided is for reference only.
Unless otherwise stated, all agents are approved for the treatment of major
depressive disorder, unipolar. | | BID = twice daily, EKG = electrocardiogram, GI = gastrointestinal, MAOI =
monoamine oxidase inhibitor, MDD = major depressive disorder, OCD =
obsessive-compulsive disorder, PMDD = premenopausal dysphoric disorder, PTSD =
post-traumatic stress disorder, SNRI = serotonin and norepinephrine reuptake
inhibitor, SSRI = selective serotonin reuptake inhibitor. |
|
16 . Which of the following is NOT an advantage of using SSRIs in the treatment of depression?
| A) | | Ease of dosing |
| B) | | Low toxicity in overdose |
| C) | | Less prominent side effect profile |
| D) | | Efficacy in initially addressing anxiety or panic symptoms |
ANTIDEPRESSANT MEDICATIONS
SSRIs are thought to act by inhibiting serotonin transporters (SERT) that reuptake serotonin (5-HT) into the presynaptic cell, increasing 5-HT in the synaptic cleft. SSRIs have advantages of low overdose lethality and better tolerability than first-generation antidepressants, which can improve adherence. SSRIs are particularly effective in patients with obsessive-compulsive symptoms, but may initially worsen anxiety or panic symptoms [35,43,44]. This class includes the agents fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), and vortioxetine (Brintellix). Escitalopram may have fewer drug-drug interactions than other SSRIs, and fluoxetine may be a better choice in patients with poorer adherence due to its long half-life [35,43,44].
17 . The large side effect profiles of tricyclic antidepressants (TCAs) are likely due to
| A) | | abuse potential. |
| B) | | toxicity at therapeutic doses. |
| C) | | central action affecting many body systems. |
| D) | | their high affinity for the H1 and H2 histamine receptors and muscarinic acetylcholine receptors. |
ANTIDEPRESSANT MEDICATIONS
TCAs are predominantly serotonin and/or norepinephrine reuptake inhibitors that act by blocking the serotonin transporter and the norepinephrine transporter, respectively, which results in an elevation of the extracellular concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. TCAs also have varying but typically high affinity for the H1 and H2 histamine receptors and muscarinic acetylcholine receptors. As a result, they also act as potent antihistamines and anticholinergics. These properties are generally undesirable in antidepressants, however, and likely contribute to their large side effect profiles [48].
18 . The restrictive diet required with oral MAOIs is due to which mechanism?
| A) | | Muscarinic receptor blockade |
| B) | | Inhibition of dietary amine catabolism |
| C) | | Antagonism of intestinal opioid receptors |
| D) | | Activation of gastrointestinal serotonin receptors |
ANTIDEPRESSANT MEDICATIONS
With oral ingestion, MAOIs inhibit the catabolism of dietary amines. When foods containing tyramine are consumed, the individual may suffer from hypertensive crisis [50]. If foods containing tryptophan are consumed, hyperserotonemia may result. The amount required to cause a reaction varies greatly from individual to individual and depends on the degree of inhibition, which in turn depends on dosage and selectivity.
19 . Which of the following antidepressants is sedating and may be superior in the treatment of depression associated with severe insomnia and anxiety?
| A) | | Sertraline |
| B) | | Fluoxetine |
| C) | | Citalopram |
| D) | | Mirtazapine |
ANTIDEPRESSANT MEDICATIONS
Mirtazapine can be very sedating and promotes appetite and weight increase, which in some patients may be desirable. It has a faster onset of action than fluoxetine, paroxetine, or sertraline, and may be superior to SSRIs in depression associated with severe insomnia and anxiety. Trazodone is also very sedating and is usually used as a sleep aid rather than as an antidepressant [35,43,44].
20 . The prevalence of sexual side effects is highest with which of the following antidepressants?
| A) | | Bupropion |
| B) | | Trazodone |
| C) | | Venlafaxine |
| D) | | Moclobemide |
ANTIDEPRESSANT MEDICATIONS
Nearly all commercially available antidepressants are associated with sexual side effects. SSRI/SNRIs show the highest rates of sexual dysfunction, including impaired sexual motivation, desire, arousal, and orgasm affecting men and women. Prescribers greatly underestimate the prevalence and patient burden of sexual side effects from antidepressants and other medications [56]. Among antidepressants, prevalence rates of sexual side effects are highest with venlafaxine and SSRIs; moderate with TCAs and MAOIs; low with bupropion, trazodone, nefazodone, mirtazapine, agomelatine, and vilazodone; and lowest with the reversible MAOI moclobemide [57,58]. As noted, gepirone is not associated with sexual dysfunction. Compared to spontaneous patient reporting, systematic inquiry increases the rate of identifying sexual side effects by ≥60% [58].
21 . Which of the following antidepressants is associated with the lowest risk of discontinuation symptoms?
| A) | | Paroxetine |
| B) | | Fluoxetine |
| C) | | Venlafaxine |
| D) | | Amitriptyline |
ANTIDEPRESSANT MEDICATIONS
Antidepressant discontinuation (more appropriately termed withdrawal) symptoms are described by the FINISH mnemonic (flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, hyperarousal), may be experienced by up to 40% of patients when antidepressants are stopped abruptly, and may occur with any antidepressant [62,63,64,65]. SSRI withdrawal symptoms are far more frequent with paroxetine. Common symptoms include dizziness, nausea, headache, confusion, low energy, weakness, sleep disturbance, flu-like symptoms, restlessness, agitation, anxiety, panic, anger, and irritability. Less common and more severe symptoms include electric-shock sensations, vertigo, paresthesia, intensified suicidal ideation, aggression, derealization, depersonalization, and visual/auditory hallucinations. Gradual tapering is a reasonable strategy but does not prevent the onset of SSRI withdrawal [66]. SSRI withdrawal syndrome is least likely with fluoxetine and vortioxetine [62].
22 . Among the antidepressants, the only agent approved for use in treating major depressive disorder in pediatric patients is
| A) | | sertraline. |
| B) | | fluoxetine. |
| C) | | fluvoxamine. |
| D) | | clomipramine. |
ANTIDEPRESSANT MEDICATIONS
Among the antidepressants, only fluoxetine is approved for use in treating major depressive disorder in pediatric patients. In addition, fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for obsessive-compulsive disorder (OCD) in pediatric patients. Other than these indications, all other use of antidepressants in children is off-label [71]. However, these off-label uses are relatively common, particularly among adolescents and pediatric patients with more severe disease.
23 . Which of the following is a contributor to treatment-resistant depression?
| A) | | Illness severity |
| B) | | Medical and psychiatric comorbidity |
| C) | | Limitations of FDA-approved drug options |
| D) | | All of the above |
ANTIDEPRESSANT MEDICATIONS
Treatment-resistant depression is a problem increasingly encountered by primary care and mental health providers. Contributors to treatment-resistant depression include illness severity, medical and psychiatric comorbidity, and the limitations of FDA-approved drug options. The definition of treatment resistance lacks consensus, but the most common definition is an inadequate response to two or more antidepressants. This does not consider adjunctive strategies or distinguish patients with partial versus non-response [62,77].
24 . What is the typical starting dose for lithium in the treatment of bipolar disorder?
| A) | | 2.5-5 mg three times per day. |
| B) | | 40 mg per day. |
| C) | | 100 mg per day. |
| D) | | 300 mg twice daily. |
MOOD STABILIZERS AND BIPOLAR DISORDER
MEDICATIONS USED IN THE TREATMENT OF BIPOLAR DISORDER
| Drug | Dose Range | Typical Starting Dose | Potential Adverse Effects | Comments |
|---|
| Lithium (Lithobid) | 600–1,800 mg/day in divided doses | 300 mg BID | Xerostomia, tremor, thyroid-stimulating hormone elevation, leukocytosis,
nausea | Lithium toxicity is closely related to serum lithium levels and can occur at
doses close to therapeutic levels. Monitoring should be available before initiating
therapy. |
| Anticonvulsants |
| Valproic acid (Divalproex) | 250–1,500 mg BID based on levels | 250–500 mg PO BID | Weight gain, hair loss, GI upset | Drug levels, complete blood count, and hepatic function should be
followed. |
| Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol) | 100–800 mg BID | 100–200 mg BID | Weight gain | Hepatic function, drug level, and CBC should be followed. |
| Lamotrigine (Lamictal, Subvenite) | Titrate to maximum 200 mg/day | 25 mg/day | Nausea, tremor, rash, Stevens Johnson syndrome | — |
| Atypical Antipsychotics |
| Aripiprazole (Abilify) | 2.5–30 mg/day | 2.5–5 mg/day | Weight gain (least likely in this class), extrapyramidal symptoms, constipation,
sedation | Available in long-acting IM formulation |
| Asenapine (Saphris, Secuado) | 2.5–10 mg BID | 2.5–5 mg PO BID | Weight gain, extrapyramidal symptoms, constipation, sedation | — |
| Cariprazine (Vraylar) | 1.5–6 mg/day | 1.5 mg/day | Weight gain, extrapyramidal symptoms, constipation, sedation | — |
| Lurasidone (Latuda) | 40–160 mg/day | 40 mg/day | Weight gain, extrapyramidal symptoms, constipation, sedation | — |
| Olanzapine (Zyprexa) | 2.5–30 mg either BID or at night | 2.5 mg/day | Weight gain (very likely), extrapyramidal symptoms, constipation,
sedation | — |
| Olanzapine/fluoxetine (Symbyax) | Up to 18 mg/day olanzapine and 75 mg/day fluoxetine | 6 mg/day olanzapine and 25 mg/day fluoxetine | Weight gain, extrapyramidal symptoms, constipation, sedation | Usually given at night |
| Quetiapine (Seroquel) | 50–800 mg/day | 50–100 mg daily or BID | Weight gain, extrapyramidal symptoms, constipation, sedation | Available in extended-release formulation |
| Risperidone (Perseris, Risperdal) | 0.5–6 mg/day (may be given BID) | 0.5–1 mg daily or BID | Weight gain, extrapyramidal symptoms, constipation, sedation, increased
prolactin, male gynecomastia | Available in long-acting IM formulation |
| Ziprasidone (Geodon) | 40–80 mg BID | 40 mg BID | Weight gain, extrapyramidal symptoms, constipation, sedation, increased
prolactin | Taken with food to improve absorption |
| BID = twice per day, CBC = complete blood count, GI
= gastrointestinal, IM = intramuscular, PO = oral. |
25 . Although all major antidepressant classes are comparably effective against anxiety disorders, which of the following is recommended due to better safety and tolerability?
| A) | | TCAs |
| B) | | Monoamine oxidase inhibitors (MAOIs) |
| C) | | Selective serotonin reuptake inhibitors (SSRIs) |
| D) | | None of the above |
SSRIs are considered first-line therapy for generalized
anxiety disorder and panic disorder [101,103]. TCAs have comparable efficacy to
SSRIs in panic disorder and generalized anxiety disorder [104,105]. TCAs are lethal in
overdose and, compared with SSRIs, have a markedly broader, more problematic, and less
tolerable side effect profile [101].
Nonetheless, TCAs may work when first-line agents do not [106]. Also, some patients with panic disorder are sensitive to both
beneficial and adverse effects of TCAs, so cannot tolerate imipramine doses >10 mg/day
but still experience panic blockade [101].
26 . The benzodiazepine with greater efficacy in panic disorder is
| A) | | diazepam. |
| B) | | lorazepam. |
| C) | | alprazolam. |
| D) | | clonazepam. |
Meta-analyses suggest alprazolam, lorazepam, and diazepam
are effective but comparable in generalized anxiety disorder efficacy, while clonazepam
shows much greater efficacy in the treatment of panic disorder than alprazolam, lorazepam,
and diazepam, which all have modest efficacy [112].
27 . Which of the following reflects inappropriate benzodiazepine prescribing?
| A) | | As-needed for ongoing treatment of chronic mild-to-moderate anxiety |
| B) | | Short-term (two to four weeks) use in patients with severe anxiety and unacceptable distress |
| C) | | For infrequent use, to permit exposure to situations evoking severe anxiety (e.g., plane travel) |
| D) | | In the initial weeks of SSRI/SNRI initiation to quickly reduce anxiety before the onset of SSRI/SNRI anxiolytic effects |
Benzodiazepine treatment of anxiety disorders is controversial. While effective in rapid anxiety reduction, the potential drawbacks with long-term use are substantial. These agents are indicated when potent, short-term anxiolytic effects are necessary to permit infrequent exposure to feared stimuli and potentially severe anxiety, such as airplane travel [103,106,113]. Clonazepam, lorazepam, and alprazolam are effective for short-term use in panic disorder, generalized anxiety disorder, and SAD, but ineffective for, and potentially worsening, comorbid depression [114]. The rapid anxiolytic effects make benzodiazepines highly appealing to patients with anxiety, but aside from this specific context, benzodiazepine prescribing for as-needed use is discouraged [106,115,116]. Benzodiazepines can reinforce pill taking, serve as a safety signal that undermines self-efficacy, and become incorporated into conditioned fear responses; these concerns are heightened with as-needed use. On-demand dosing links pill taking to rapid anxiety reduction, powerfully reinforcing avoidance in anxiety-provoking situations and encouraging longer-term reliance on the drug. This iatrogenic effect also contributes to poor response to cognitive-behavioral therapy.
The current recommended prescribing is for time-dependent use, instead of panic response-dependent use, to minimize the risks [103]. This would also seem to maximize risk of withdrawal syndrome from uninterrupted versus intermittent drug exposure.
Benzodiazepines are also useful in the initial weeks of SSRI/SNRI initiation to rapidly reduce anxiety and possible early anxiogenic medication side effects before the onset of SSRI/SNRI anxiolytic effects [103,106,113]. However, patients may discontinue the antidepressant when co-prescribed a rapidly effective benzodiazepine, believing the benzodiazepine's symptom relief makes the SSRI/SNRI unneeded. Supportive therapy with regular visits or phone contacts may also help patients remain adherent until the delayed onset of antidepressant benefits appears or early antidepressant side effects lessen [117].
Another indication for benzodiazepine use is for the short-term relief (two to four weeks only) of anxiety that is severe, disabling, or subjecting the individual to unacceptable distress. Perhaps the greatest prescribing challenge with benzodiazepines is preventing short-term use from insidiously developing into long-term use. Patients with the most severe anxiety may obtain the greatest relief and become most hesitant to discontinue use [118]. In many cases, clinicians ignore the recommended two- to four-week prescribing limit, mainly because alternative options with superior anxiolytic effects are not available [119]. Clinicians intending to prescribe alprazolam should carefully consider the likelihood that its use will remain restricted to the very short term—a few days to a couple weeks—to see the patient through a crisis [118].
28 . Long-term benzodiazepine use can result in added symptoms during stable-dose maintenance. Which of the following is one of these symptoms?
| A) | | Weight gain |
| B) | | Hypotension |
| C) | | Increasing anxiety |
| D) | | Extrapyramidal reactions |
Long-term benzodiazepine use can result in added symptoms during stable-dose maintenance, including increasing anxiety and withdrawal-associated symptoms such as perceptual disturbances and paresthesia. This emerging withdrawal syndrome despite ongoing benzodiazepine use is much more likely with highly potent and rapidly eliminated alprazolam or lorazepam and is temporarily alleviated by dose escalation. As craving, dysphoria, and other withdrawal symptoms develop over time between doses, the motivation to continue benzodiazepine use for anxiolysis gradually merges with the need to avoid withdrawal symptoms [124].
29 . Despite comparable dosing, patients with which anxiety disorder often show greater difficulty tapering off of benzodiazepines?
| A) | | Agoraphobia |
| B) | | Panic disorder |
| C) | | Specific phobia |
| D) | | Generalized anxiety disorder |
Despite comparable dosing, patients with panic disorder often show greater difficulty tapering than patients with generalized anxiety disorder. Problems during alprazolam tapering are most severe during the last half of the taper. Patients with panic disorder receiving diazepam or alprazolam had fewer problems during taper of the top 50% of daily dose. However, with abrupt discontinuation of the remaining dose, alprazolam caused significantly more anxiety, relapse, and rebound. This may reflect greater problems withdrawing from short half-life, high-potency benzodiazepines like alprazolam [43].
30 . Which of the following agents is approved for the treatment of alcohol use disorder?
| A) | | Buprenorphine |
| B) | | Bupropion |
| C) | | Varenicline |
| D) | | Acamprosate |
PHARMACOTHERAPY FOR SUBSTANCE USE DISORDERS
MEDICATIONS USED IN THE TREATMENT OF SUBSTANCE USE DISORDERS
| Drug | Dose Range | Typical Starting Dose | Potential Adverse Effects | Route(s) |
|---|
| Opioid Use Disorder |
| Buprenorphine/naloxone (Bunavail, Suboxone, Zubsolv) |
| Buprenorphine: 0.7–24 mg/day | | Naloxone: 0.18–6 mg/day |
| 4/1 mg/day | Pain, headache, nausea, diaphoresis | Buccal film, sublingual film, sublingual tablet |
| Methadone (Dolophine, Methadose, DISKETS) | 20–120 mg/day | 20–30 mg/day | Pruritus, constipation, cardiac abnormalities | PO, IV |
| Naltrexone (Vivitrol) |
| PO: 25–50 mg/day | | IM: 380 mg/week |
|
| PO: 25 mg/day | | IM: 380 mg/week |
| Injection site reactions, anxiety, syncope | PO, IM |
| Buprenorphine (Belbuca, Buprenex, Butrans, Probuphine, Sublocade) |
| SQ: 100–300 mg/month | | SL:2–24 mg/day |
|
| SQ: 300 mg/month | | Implant: 4 implants | | SL:2–4 mg/day |
| Few | Sublingual tablet, subdermal implant, SQ injection |
| Alcohol Use Disorder |
| Acamprosate (Campral) | 666 mg TID | 666 mg TID | Diarrhea | PO |
| Naltrexone (Vivitrol) |
| PO: 25–100 mg/day | | IM: 380 mg/month |
|
| PO: 50 mg/day | | IM: 380 mg/month |
| Injection site reactions, anxiety, syncope | PO, IM |
| Disulfiram | 125–500 mg/day | 250 mg/day | Bitter taste, impotence, drowsiness | PO |
| Nicotine Use Disorder |
| Bupropion, sustained-release (Zyban) | 150 mg daily or BID | 150 mg/day | Weight loss, constipation, agitation, xerostomia, nausea | PO |
| Nicotine |
| Gum: Up to a maximum 30 pieces/day | | Inhaler: 6–16 cartridges/day | | Lozenge: Titrate to 1 lozenge every 4 to 8 hours | | Nasal spray: Maximum 80 sprays/day | | Patch: One patch/day for 8 weeks |
|
| Gum: 1 to 2 pieces/hour (2 mg/piece) | | Inhaler: 6 cartridges/day | | Lozenge: One lozenge every 1 to 2 hours | | Nasal spray: 1 spray in each nostril once or twice per hour | | Patch: One patch/day |
| Oral irritation, headache, dyspepsia, nasal discomfort, cough, rhinitis | PO, intranasal, transdermal |
| Varenicline (Chantix)a | 1 mg BID up to 12 weeks | 0.5 mg/day | Nausea, abnormal dreams, headache | PO |
| BID = two times per day, IM = intramuscular, IV = intravenous, PO = oral, SL
= sublingual, SQ = subcutaneous, TID = three times per day. | | aVarenicline production was halted and lots were
voluntary recalled in 2021 due to unacceptable levels of nitrosamines. |
|
