AUVELITY

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)] . AUVELITY is not approved for use in pediatric patients [see Use in Specific Populations (8.4)] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. AUVELITY is not approved for use in pediatric patients. ( 5.1 , 8.4 )

5 WARNINGS AND PRECAUTIONS Seizure: Risk is dose-related. Discontinue if seizure occurs. ( 4 , 5.2 ) Increased Blood Pressure and Hypertension: AUVELITY can increase blood pressure and cause hypertension. Assess blood pressure before initiating treatment and monitor periodically during treatment. ( 5.3 ) Activation of Mania or Hypomania: Screen patients for bipolar disorder. ( 5.4 ) Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare provider if such reactions occur. ( 5.5 ) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. ( 5.6 ) Dizziness: AUVELITY may cause dizziness. Take precautions to reduce falls and use caution when operating machinery. ( 5.7 ) Serotonin Syndrome: Use of AUVELITY with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants increases the risk. Discontinue if occurs. ( 5.8 , 7.1 ) Embryo-fetal Toxicity: May cause fetal harm. Advise pregnant females of the potential risk to a fetus. Discontinue treatment in pregnant females and use alternative treatment for females who are planning to become pregnant. ( 5.9 , 8.1 , 8.3 ) Hyponatremia: Can occur in association with SIADH. ( 5.10 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behavior in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients *AUVELITY is not approved for use in pediatric patients. Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18-24 years old 5 additional patients Decreases Compared to Placebo 25-64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing AUVELITY, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Seizure Bupropion, a component of AUVELITY, can cause seizure. The risk of seizure with bupropion is dose-related. When a bupropion hydrochloride (HCl) sustained-release tablet was dosed up to 300 mg per day (approximately 1.5 times the maximum recommended daily dosage of AUVELITY), the incidence of seizure was approximately 0.1% (1/1,000) and increased to approximately 0.4% (4/1,000) at the maximum recommended dosage for the sustained-release tablet of 400 mg per day (approximately 2 times the maximum recommended daily dosage of AUVELITY). The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with AUVELITY. AUVELITY is contraindicated in patients with a seizure disorder, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . The following conditions can also increase the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor or CNS infection; severe stroke; concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids); metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia); use of illicit drugs (e.g., cocaine); or abuse or misuse of prescription drugs such as CNS stimulants. Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin; use of anorectic drugs; and excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates. Because the risk of seizure with bupropion is dose-related, screen patients for use of other bupropion-containing products prior to initiating AUVELITY [see Dosage and Administration ( 2.1 )] . If concomitant use of AUVELITY with other bupropion-containing products is clinically warranted, inform patients of the risk. Discontinue AUVELITY and do not restart treatment if the patient experiences a seizure. 5.3 Increased Blood Pressure and Hypertension AUVELITY contains bupropion, which can cause elevated blood pressure and hypertension. The risk of hypertension is increased if AUVELITY is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . Data from a comparative trial of a sustained-release tablet formulation of bupropion HCl, nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of hypertension in patients treated with the combination of sustained-release bupropion and NTS. In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had hypertension compared with 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension compared with none of the subjects treated with sustained-release bupropion or placebo. Monitor blood pressure in patients who receive the combination of bupropion and nicotine replacement. In a clinical trial of an immediate-release bupropion tablet formulation in MDD subjects with stable congestive heart failure (N=36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects, leading to discontinuation of bupropion treatment. There are no controlled trials assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease. Assess blood pressure prior to initiating treatment, and periodically monitor blood pressure during treatment with AUVELITY [see Dosage and Administration ( 2.1 )] . 5.4 Activation of Mania or Hypomania Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to initiating AUVELITY, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression) [see Dosage and Administration ( 2.1 )] . AUVELITY is not approved for use in treating bipolar depression. 5.5 Psychosis and Other Neuropsychiatric Reactions AUVELITY contains bupropion. Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. AUVELITY contains dextromethorphan. Dextromethorphan overdose can cause toxic psychosis, stupor, coma, and hyperexcitability [see Overdosage ( 10 )] . Because the risks of neuropsychiatric reactions are dose-related, screen patients for use of other bupropion- or dextromethorphan-containing products prior to initiating AUVELITY. If concomitant use of AUVELITY with other bupropion- or dextromethorphan-containing products is clinically warranted, monitor patients for neuropsychiatric reactions [see Dosage and Administration ( 2.1 )] and instruct patients to contact a healthcare provider if such reactions occur. 5.6 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including bupropion, a component of AUVELITY, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including AUVELITY, in patients with untreated anatomically narrow angles. 5.7 Dizziness AUVELITY may cause dizziness [see Adverse Reactions ( 6.1 )] . In controlled studies of AUVELITY in depression, 14% of patients receiving AUVELITY and 6% of patients on placebo experienced dizziness. In a short-term controlled study of AUVELITY in agitation associated with dementia due to Alzheimer’s disease, 9% of patients receiving AUVELITY and 3% of patients on placebo experienced dizziness. Take precautions to reduce the risk of falls, particularly for patients with motor impairment affecting gait or those with a history of falls. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that AUVELITY therapy does not affect them adversely. 5.8 Serotonin Syndrome AUVELITY contains dextromethorphan. Concomitant use of AUVELITY with SSRIs or tricyclic antidepressants may cause serotonin syndrome, a potentially life-threatening condition with changes including altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor [see Drug Interactions ( 7.1 ), Overdosage ( 10 )] . The concomitant use of AUVELITY with MAOIs is contraindicated. In addition, do not initiate AUVELITY in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking AUVELITY discontinue AUVELITY before initiating treatment with the MAOI [see Contraindications ( 4 ), Drug Interactions ( 7 )] . Prior to initiating AUVELITY, screen patients for use of other dextromethorphan-containing products [see Dosage and Administration ( 2.1 )] . If concomitant use of AUVELITY with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. Discontinue AUVELITY and/or concomitant serotonergic drug immediately if the above symptoms occur, and initiate supportive symptomatic treatment. 5.9 Embryo-fetal Toxicity Based on animal studies, AUVELITY may cause fetal harm when administered during pregnancy. In developmental toxicity studies in rats and rabbits, when a combination of dextromethorphan/quinidine was given to pregnant animals, fetal malformations (rabbits) and embryolethality were demonstrated in offspring. Neurotoxicity findings were observed in juvenile rats treated with a combination of dextromethorphan/quinidine on postnatal day (PND) 7, which corresponds to the third trimester of gestation through the first few months of life and may extend through the first three years of life in humans. The separate effect of dextromethorphan on developmental toxicity at the recommended clinical dose is unclear. Discontinue treatment in pregnant females and advise the patient about the potential risk to a fetus. Use alternative treatment for females who are planning to become pregnant [see Use in Specific Populations ( 8.1 , 8.3 )] . 5.10 Hyponatremia Hyponatremia has occurred as a result of treatment with AUVELITY. One case with serum sodium of 115 mmol/L was reported in a subject treated with AUVELITY in a premarketing clinical study. Geriatric patients may be at greater risk of developing hyponatremia. Hyponatremia may be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Concomitant use of Auvelity with a serotonergic antidepressant may increase the risk of hyponatremia. Also, patients taking diuretics or who are otherwise volume-depleted can be at greater risk. Discontinue AUVELITY in patients with symptomatic hyponatremia and institute appropriate medical intervention. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. More severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. [see Use in Specific Populations (Section 8.5 )]

<table width="785"><caption> Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behavior in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients</caption><colgroup><col width="40%"/><col width="60%"/></colgroup><tfoot><tr><td colspan="2"><paragraph styleCode="First Footnote">*AUVELITY is not approved for use in pediatric patients.</paragraph></td></tr></tfoot><tbody><tr><td styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold"> Age Range</content></td><td styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated</content></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"/><td styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold"> Increases Compared to Placebo</content></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule">&lt;18 years old</td><td styleCode="Botrule Lrule Rrule Toprule">14 additional patients</td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule">18-24 years old</td><td styleCode="Botrule Lrule Rrule Toprule">5 additional patients</td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"/><td styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold"> Decreases Compared to Placebo</content></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule">25-64 years old</td><td styleCode="Botrule Lrule Rrule Toprule">1 fewer patient</td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule">&#x2265;65 years old</td><td styleCode="Botrule Lrule Rrule Toprule">6 fewer patients</td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions ( 5.1 )] Seizure [see Warnings and Precautions ( 5.2 )] Increased Blood Pressure and Hypertension [see Warnings and Precautions ( 5.3 )] Activation of Mania or Hypomania [see Warnings and Precautions ( 5.4 )] Psychosis and Other Neuropsychiatric Reactions [see Warnings and Precautions ( 5.5 )] Angle-closure Glaucoma [see Warnings and Precautions ( 5.6 )] Dizziness [see Warnings and Precautions ( 5.7 )] Serotonin Syndrome [see Warnings and Precautions ( 5.8 )] Embryo-fetal Toxicity [see Warnings and Precautions ( 5.9 )] Hyponatremia [see Warnings and Precautions ( 5.10 )] MDD: Most common adverse reactions (≥5% and more than twice as frequently as placebo): dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. (6.1) Agitation associated with dementia due to Alzheimer’s disease: Most common adverse reactions (≥5% and more than twice as frequently as placebo): dizziness and dyspepsia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Axsome Therapeutics at 1-800-484-1672 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. AUVELITY has been evaluated for safety in 2,550 adult patients who participated in multiple-dose clinical trials for major depressive disorder, agitation associated with dementia due to Alzheimers disease, or another indication. Among them, 918 patients were treated with AUVELITY for at least 6 months, and 251 patients were treated with AUVELITY for at least 1 year. Major Depressive Disorder The data below are based on the 6-week, placebo-controlled study in which either AUVELITY (n=162) or placebo (n=164) was administered twice daily to patients with MDD (Study 1). Demographics of the patients who participated in this study are summarized in Clinical Studies [see Clinical Studies (Section 14.1 )]. Adverse Reactions Leading to Discontinuation In the 6-week placebo-controlled study, 4% of patients treated with AUVELITY and 0% of placebo-treated patients discontinued participation due to adverse reactions. The adverse reaction that led to study discontinuation in 1% of patients treated with AUVELITY was anxiety (2%). Most Common Adverse Reactions In the 6-week placebo-controlled clinical study, the most common (incidence 5% for AUVELITY and more than twice as frequently as placebo) adverse reactions were dizziness (16%), headache (8%), diarrhea (7%), somnolence (7%), dry mouth (6%), sexual dysfunction (6%), and hyperhidrosis (5%). Table 2 shows the incidence of adverse reactions that occurred in 2% of patients treated with AUVELITY and more frequently than in patients treated with placebo in Study 1. Table 2: Adverse Reactions Occurring in ≥2% of Adult Patients with MDD Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 6-Week Placebo-Controlled Study (Study 1) a Sexual dysfunction includes orgasm abnormal, erectile dysfunction, libido decreased, anorgasmia b Fatigue includes fatigue, lethargy c Paraesthesia includes paraesthesia, hypoaesthesia Adverse Reaction AUVELITY (N=162) % Placebo (N=164) % Dizziness 16 6 Nausea 13 9 Headache 8 4 Diarrhea 7 3 Somnolence 7 3 Dry mouth 6 2 Sexual dysfunction a 6 0 Hyperhidrosis 5 0 Anxiety 4 1 Constipation 4 2 Decreased appetite 4 1 Insomnia 4 2 Arthralgia 3 0 Fatigue b 3 2 Paraesthesia c 3 0 Vision blurred 3 0 Agitation Associated with Dementia Due to Alzheimers Disease The data below are based on the 5-week, placebo-controlled, parallel-group study in which either AUVELITY (n=159) or placebo (n=158) was administered twice daily to patients with agitation associated with dementia due to Alzheimers disease. [see Clinical Studies (Section 14.2 )] Adverse Reactions Leading to Discontinuation In the 5-week placebo-controlled study, 1.3% of patients treated with AUVELITY and 1.3% of placebo-treated patients discontinued participation due to adverse reactions. No individual adverse reaction leading to discontinuation occurred in more than one subject. Most Common Adverse Reactions In the 5-week placebo-controlled clinical study, the most common (incidence 5% for AUVELITY and more than twice as frequently as placebo) adverse reactions consisted of dizziness (9%) and dyspepsia (6%). Table 3 shows the incidence of adverse reactions that occurred in 2% of patients treated with AUVELITY and more frequently than in patients treated with placebo in a 5-week placebo-controlled study (Study 3). Table 3: Adverse Reactions Occurring in ≥2% of Adult Patients with Agitation Associated with Dementia Due to Alzheimer’s Disease Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 5-Week Placebo-Controlled Study (Study 3) a Dizziness includes Vertigo, Dizziness postural, Balance disorder. b Somnolence includes Somnolence, Hypersomnia. c Dyspepsia includes Abdominal discomfort, Dyspepsia, Gastritis, Abdominal pain upper, Gastroesophageal reflux disease. d Fatigue includes Asthenia, Lethargy, Fatigue. e Nausea includes Nausea, Vomiting. f Psychotic symptom includes Catatonia, Delusion, Hallucination, Hallucination visual. g Confusional State includes Confusional state, Delirium, Disorientation. h Bacterial infection includes Abscess limb, Staphylococcal infection, Urinary tract infection. Adverse Reaction AUVELITY (N=159) % Placebo (N=158) % Dizziness a 9 3 Somnolence b 8 4 Dyspepsiac 6 1 Fatigue d 6 3 Nausea e 5 3 Dry Mouth 4 3 Headache 4 3 Constipation 3 0 Psychotic symptom f 3 0 Confusional state g 3 1 Cough 3 1 Bacterial infection h 3 1 6.2 Postmarketing Experience The following adverse reactions have been identified with the use of theAUVELITY and its individual components of AUVELITY, dextromethorphan and bupropion, during postmarketing use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. AUVELITY: Feeling abnormal, tinnitus, and tremor. Dextromethorphan Drowsiness, dizziness, nervousness or restlessness, nausea, vomiting, and stomach pain. Bupropion Body (General) : Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness. Cardiovascular: Complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, pulmonary embolism, and Brugada pattern/syndrome. Digestive: Colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, pancreatitis, and stomach ulcer. Endocrine: Hyperglycemia, hypoglycemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion. Hemic and Lymphatic: Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin. Metabolic and Nutritional: Glycosuria. Musculoskeletal: Muscle rigidity/fever/rhabdomyolysis and muscle weakness. Nervous System: Abnormal electroencephalogram (EEG), aggression, agitation, akinesia, aphasia, coma, completed suicide, delirium, delusions, depression, dysarthria, euphoria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, homicidal ideation, hostility, increased libido, manic reaction, neuralgia, neuropathy, panic, paranoid ideation, psychosis, restlessness, suicide ideation, suicide attempt, unmasking tardive dyskinesia, aseptic meningitis, and tremor. Respiratory: Pneumonia. Skin and subcutaneous tissue disorders: Alopecia, angioedema, exfoliative dermatitis, hirsutism, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Special Senses: Deafness, increased intraocular pressure, mydriasis, and tinnitus. Urogenital : Abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.

<table width="785px"><caption>Table 2: Adverse Reactions Occurring in &#x2265;2% of Adult Patients with MDD Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 6-Week Placebo-Controlled Study (Study 1) </caption><colgroup><col width="33.4%"/><col width="33.3%"/><col width="33.3%"/></colgroup><tfoot><tr styleCode="First Last"><td colspan="3"><paragraph styleCode="First Footnote">^aSexual dysfunction includes orgasm abnormal, erectile dysfunction, libido decreased, anorgasmia</paragraph><paragraph styleCode="Footnote">^bFatigue includes fatigue, lethargy</paragraph><paragraph styleCode="Footnote">^cParaesthesia includes paraesthesia, hypoaesthesia</paragraph></td></tr></tfoot><tbody><tr><td><content styleCode="bold"> Adverse Reaction</content></td><td align="center"><paragraph><content styleCode="bold">AUVELITY</content> <content styleCode="bold">(N=162)</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center"><paragraph><content styleCode="bold"> Placebo</content> <content styleCode="bold">(N=164)</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td>Dizziness</td><td align="center">16</td><td align="center">6</td></tr><tr><td>Nausea</td><td align="center">13</td><td align="center">9</td></tr><tr><td>Headache</td><td align="center">8</td><td align="center">4</td></tr><tr><td>Diarrhea</td><td align="center">7</td><td align="center">3</td></tr><tr><td>Somnolence</td><td align="center">7</td><td align="center">3</td></tr><tr><td>Dry mouth</td><td align="center">6</td><td align="center">2</td></tr><tr><td>Sexual dysfunction^a</td><td align="center">6</td><td align="center">0</td></tr><tr><td>Hyperhidrosis</td><td align="center">5</td><td align="center">0</td></tr><tr><td>Anxiety</td><td align="center">4</td><td align="center">1</td></tr><tr><td>Constipation</td><td align="center">4</td><td align="center">2</td></tr><tr><td>Decreased appetite</td><td align="center">4</td><td align="center">1</td></tr><tr><td>Insomnia</td><td align="center">4</td><td align="center">2</td></tr><tr><td>Arthralgia</td><td align="center">3</td><td align="center">0</td></tr><tr><td>Fatigue^b</td><td align="center">3</td><td align="center">2</td></tr><tr><td>Paraesthesia^c</td><td align="center">3</td><td align="center">0</td></tr><tr><td>Vision blurred</td><td align="center">3</td><td align="center">0</td></tr></tbody></table>

<table><caption>Table 3: Adverse Reactions Occurring in &#x2265;2% of Adult Patients with Agitation Associated with Dementia Due to Alzheimer&#x2019;s Disease Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 5-Week Placebo-Controlled Study (Study 3)</caption><colgroup><col width="33.4%"/><col width="33.3%"/><col width="33.3%"/></colgroup><tfoot><tr styleCode="First Last"><td colspan="3">^a Dizziness includes Vertigo, Dizziness postural, Balance disorder. ^b Somnolence includes Somnolence, Hypersomnia. ^c Dyspepsia includes Abdominal discomfort, Dyspepsia, Gastritis, Abdominal pain upper, Gastroesophageal reflux disease. ^d Fatigue includes Asthenia, Lethargy, Fatigue. ^e Nausea includes Nausea, Vomiting. ^f Psychotic symptom includes Catatonia, Delusion, Hallucination, Hallucination visual. ^g Confusional State includes Confusional state, Delirium, Disorientation. ^h Bacterial infection includes Abscess limb, Staphylococcal infection, Urinary tract infection.</td></tr></tfoot><tbody><tr><td>Adverse Reaction</td><td align="center"><paragraph>AUVELITY (N=159)</paragraph><paragraph>%</paragraph></td><td align="center"><paragraph>Placebo (N=158)</paragraph><paragraph>%</paragraph></td></tr><tr><td>Dizziness^a</td><td align="center">9</td><td align="center">3</td></tr><tr><td>Somnolence^b</td><td align="center">8</td><td align="center">4</td></tr><tr><td>Dyspepsiac</td><td align="center">6</td><td align="center">1</td></tr><tr><td>Fatigue^d</td><td align="center">6</td><td align="center">3</td></tr><tr><td>Nausea^e</td><td align="center">5</td><td align="center">3</td></tr><tr><td>Dry Mouth</td><td align="center">4</td><td align="center">3</td></tr><tr><td>Headache</td><td align="center">4</td><td align="center">3</td></tr><tr><td>Constipation</td><td align="center">3</td><td align="center">0</td></tr><tr><td>Psychotic symptom^f</td><td align="center">3</td><td align="center">0</td></tr><tr><td>Confusional state^g</td><td align="center">3</td><td align="center">1</td></tr><tr><td>Cough</td><td align="center">3</td><td align="center">1</td></tr><tr><td>Bacterial infection^h</td><td align="center">3</td><td align="center">1</td></tr></tbody></table>