Part 1 of this article (Psychiatric Times, July 2007, page 14), discussed a general approach to treating psychiatric emergencies in patients with bipolar and related disorders, as well as the assessment and management of agitation and impulsive aggression. Part 2 focuses on psychosis, suicidality, and specific treatments relevant to patients in emergency settings who are agitated or have bipolar disorder.
Psychosis Clinical presentation
Psychosis is diagnostically nonspecific. In a patient who is prone to psychosis, any condition that can produce severe agitation can also induce psychosis. Psychosis can be caused by bipolar disorder itself, complications or treatment of bipolar disorder, or other medical or toxic conditions. Table 1 lists some medical and psychiatric conditions that may be associated with psychosis.
Understanding the episode
A psychotic episode has 3 basic aspects: characteristics of the illness producing it, characteristics of the patient who is having the episode, and characteristics of the conditions associated with the specific episode.1 Clinicians must understand these characteristics so that effective initial and follow-up treatment can take place.
The illness. Psychotic episodes may occur as part of the natural history of an illness that produces susceptibility to psychosis, as part of an acute illness, or as part of an acute illness that is superimposed on a chronic illness that produces susceptibility to psychosis. In treating patients with bipolar disorder, it is especially important to be aware of this third possibility. Patients with bi-polar disorder are at risk for psychotic exacerbations because of drug intoxication or withdrawal, metabolic or neurological effects of medications, or endocrine disturbances that may be more common in bipolar disorder.2
Psychotic episodes in bipolar disorder, whether depressive or manic, have prodromes that may resemble those of any severe manic or depressive episode.3 Symptoms include changes in goal-directed activity, sleep, interpersonal behavior, or mood.4 In addition, characteristic prodromes of psychotic episodes include changes in sleep; activation; or sensory perception, including signs of overstimulation. For example, a patient may describe colors or sounds as being more vivid than usual, may be unable to ignore irrelevant environmental stimuli, or may begin to attribute meaning to random environmental events. Although these characteristics are general among psychotic episodes, in many psychiatric illnesses, the specific content and context, as noted in the next section, come from the life of the patient.
The individual. While the overall form of a psychotic episode may be similar for thousands of patients, the content of the delusions and hallucinations comes from the patient's life experience.1 Most patients with bipolar disorder have mood-congruent delusions and/or hallucinations; that is, the content is clearly related to the patient's affective state and usually to themes in his or her life that otherwise express themselves in a more mundane manner. However, a substantial minority of patients with bipolar disorder has psychoses with mood-incongruent delusions and/or hallucinations. These patients tend to have a more severe course of illness with more psychosocial impairment.5
The episode. Psychotic episodes result from the interaction between the patient's illness and its context. Psychotic episodes, in terms of global symptoms and time course, may be quite similar across many patients. Similarly, the generic circumstances associated with the likelihood of a psychotic episode may be similar across a large population, such as first manic or depressive episodes occurring during adolescence or childhood, postpartum epi- sodes, overstimulation, or affective episodes combined with substance use. Specific circumstances that have a high risk of recurrence of illness or psychotic episode are also based on the patient's specific experiences. For example, they may be associated with a recurring stressor or conflict in the patient's life or circumstances related to an earlier traumatic event.6
The initial pharmacological and nonpharmacological management of psychosis is essentially analogous to that of severe agitation (discussed below). Subsequent treatment is more dependent on the diagnosis. Differential diagnosis is also important because of the need to treat medical conditions that can be associated with psychosis.
Suicidality Suicide risk factors
As many as 10% to 15% of patients with bipolar disorder may eventually commit suicide, and at least 25% of completed suicides in the United States are by patients with bipolar disorder.7Table 2 summarizes clinical characteristics that are associated with risk of suicide. These characteristics identify people in whom the lifetime risk of suicide may be increased but do not define a person's risk of suicide at any specific time.
Lifetime risk increases progressively as patients exhibit more of the characteristics listed in Table 2. As discussed next, suicide risk at a given time is a result of the interaction between these lifetime risks and the acute context.
The structure of suicidal acts
The prediction of specific suicidal acts is usually based on models that combine the patient's wish to die with the opportunity or inclination to carry out the act.8 In practical terms, suicidal behavior can be a result of a combination of depression and impulsivity. Hopelessness is the aspect of depression that is most severely associated with suicide.9
The combination of impulsivity and hopelessness is dangerous.10 Suicide attempts can vary from being predominantly premeditated, with prominent depression and feelings of hopelessness, to predominantly impulsive, with much less prominent depression but with the possibility of feeling hopeless without severe depression.11
In a person who is experiencing severe hopelessness and depression, any circumstance that increases impulsivity even slightly can markedly increase the risk of suicide, potentially leading to a suicidal act that may have been planned for months or years. Therefore, acute environmental stress, overstimulation, drug- or medicine-induced activation, sleep deprivation, or any other source of agitation can be associated with an increased risk of severe suicidal behavior.12
Conversely, in a highly impulsive person, a small increase in hopelessness can markedly increase the likelihood of self-destructive and suicidal behaviors. This is exacerbated by the fact that impulsivity is associated with lack of orientation for the future and with a tendency to give up when faced with adverse or complex situations.13 Thus, the impulsive person is predisposed to hopelessness in the relative absence of depression. Therefore, in predominantly impulsive suicide attempts, the severity of the method or injury may appear to have little to do with precipitating events. For example, a severely impulsive person may shoot himself as a result of a minor romantic setback or social slight.14
Substance abuse has both direct and indirect effects on suicide risk. Patients with comorbid substance abuse and bipolar disorder are at higher risk for suicide or suicidal behavior than are patients with either disorder alone. In addition, substance abuse is associated with higher risk of being a victim of violence,15 which, in turn, is associated with higher risk of suicide or suicidal behavior.16
Mixed states in bipolar disorder require special vigilance from clinicians.17 Mixed mania combines the impulsivity and activation of mania with depression and hopelessness that may be obscured by the more prominent manic behavior. Mixed depressions combine hopelessness and depression with the impulsivity of hypomania. Mixed states have more severe autonomic arousal than is the case in mania or depression alone.18 Affective states can shift within an episode19: mixed mania can arise out of mania and mixed depression can arise out of depression, with increased risk of suicide in both cases. In a shorter time frame, mood lability can increase the risk of suicide for similar reasons.
The danger of suicide is increased early in recovery from depressive or manic episodes20 or after recent discharge from hospitals or emergency departments (EDs).21 Functional recovery from an episode of illness takes longer than syndromal recovery.22 After being discharged from the hospital or having a reduction in intensity of treatment, patients face increased environmental stressors and stimulation at a time when apparent symptomatic improvement can lead to complacency. Depression or mixed states can follow manic episodes, and periods of activation or lability can occur late in depressive episodes, perhaps even more so if patients are being treated with antidepressants.20,23
Approach to the suicidal patient
Physicians should assume that any patient seen in an emergency setting has the potential for suicidal behavior.24 Suicidality is also prevalent in nonpsychiatric patients presenting in the ED.15 With the exception of patients who have been rescued from suicide or have been brought in against their will, patients who are suicidal and present in the ED generally have some ambivalence about the act.
The physician must create a situation in which it is possible to elicit a history of the factors that contribute to suicide risk. It is generally reassuring to the patient who is suicidal and fearful to be asked questions directly, with competence and empathy, about his worst fears. It is unlikely that a patient has ever gotten the idea of suicide from being asked about it by a physician. It is equally important to understand the source of the patient's ambivalence—in other words, what it is that is keeping the patient alive.
General principles in interviewing a suicidal patient include24:
- Creating an environment in which the patient can talk about his worst fears: a setting with privacy, safety, reduced environmental noise, and an arrangement with the patient and physician seated on equal levels.
- Showing, in as many ways as possible, that the patient's situation is not as hopeless as he sees it, but that depression or other circumstances are temporary and treatable. Rather than lecturing or arguing with the patient, show this to him in every way possible. For example, when asking about the patient's loss of interest or pleasure, ask, "What do you usually like to do?" rather than "What did you like to do before you were depressed?"
- Asking the patient directly about feelings of hopelessness, wish to die, suicidal thoughts, and suicidal plans.
- If there are suicidal plans, determining how lethal the patient thinks they would be, as well as how lethal you think they are.
- Determining what steps the patient has taken toward carrying out the plan.
- If the patient has a plan and has obtained the means to carry out the plan but has not done so, determining why he has not and what circumstances would be required for him to see the plan through.
- Looking for verbal or nonverbal clues that show that the patient is no longer thinking about the future.
- Doing whatever possible to alleviate the patient's fear of loss of control. For example, if you think hospitalization is required, couch it in terms of allowing the patient to get control over his behavior and life, rather than as an attempt to control the patient.
- When assessing social supports and incorporating them into the patient's treatment strategy, remembering that even those who care deeply about the patient may become angry, ambivalent, or just need a rest from the situation.
- Taking pharmacological and nonpharmacological steps to reduce overstimulation, overactivation, and behavioral lability.
Acute Treatment Strategies
Acute treatments are those that can be used for relatively rapid treatment of severe or potentially severe behavioral disturbances. These treatments, in some cases, may also be useful in the longer term. Many treatments that are effective in patients with bipolar disorder have a more gradual onset of action, rendering them less useful for acute treatment. Under certain circumstances, however, treatment with these agents may be started in the emergency setting if the patient is known to have a diagnosis that will require longer-term treatment, if acute behavioral effects are not expected to increase behavioral problems, and if it can be assured that the patient's treatment response will be monitored.
Antipsychotics.Antipsychotic agents are among the most effective means of pharmacologically reducing overstimulation and are considered to be effective in treating aggression in a wide range of conditions usually associated with psychosis or mania.25 The usefulness of conventional antipsychotic agents is limited by extrapyramidal effects and akathisia. There is also a risk of hyperthermia or neuroleptic malignant syndrome, especially in patients who are restrained and struggling in poorly ventilated seclusion rooms.
These problems can also occur with second-generation antipsychotics. Treatment should be aimed at specific symptoms rather than used for "chemical restraint."26,27 Droperidol has been reported to be effective for relatively rapid stabilization of acute agitation and psychosis.28
Atypical antipsychotics, including clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, have the potential for effectiveness comparable to that of conventional antipsychotics but have the advantage of reducing the incidence of movement disorders. It is important, however, to note that severe movement-related disorders, most notably akathisia, can occur with atypical antipsychotic agents, as can neuroleptic malignant syndrome.29-31 Atypical antipsychotics are a heterogeneous group of medications with adverse effects that vary widely. Table 3 summarizes some properties of atypicals that are relevant to emergency treatment, compared with haloperidol. When choosing medicine, clinicians should consider the impact of its side-effect profile on the tolerability of the specific patient, especially if long-term treatment is anticipated.32
1. Cuesta MJ, Gil P, Artamendi M, et al. Premorbid personality and psychopathological dimensions in first-episode psychosis. Schizophr Res. 2002;58:273-280.
2. Krauthammer C, Klerman GL. Secondary mania: manic syndromes associated with antecedent physical illnesses or drugs. Arch Gen Psychiatry. 1978;35: 1333-1339.
3. Fava GA, Kellner R. Prodromal symptoms in affective disorders. Am J Psychiatry. 1991;148:823-830.
4. Lam D, Wong G, Sham P. Prodromes, coping strategies and course of illness in bipolar affective disorder--a naturalistic study. Psychol Med. 2001;31:1397-1402.
5. Miklowitz DJ. Longitudinal outcome and medication noncompliance among manic patients with and without mood-incongruent psychotic features. J Nerv Ment Dis. 1992;180:703-711.
6. Lieberman PB, Strauss JS. The recurrence of mania: environmental factors and medical treatment. Am J Psychiatry. 1984;141:77-80.
7. Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry. 2000;61(suppl 9):47-51.
8. Mann JJ, Waternaux C, Haas GL, Malone KM. Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry. 1999;156:181-189.
9. Beck AT, Steer RA, Kovacs M, Garrison B. Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. Am J Psychiatry. 1985;142:559-563.
10. Swann AC, Dougherty DM, Pazzaglia PJ, et al. Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder. Am J Psychiatry. 2005;162:1680-1687.
11. Simon TR, Swann AC, Powell KE, et al. Characteristics of impulsive suicide attempts and attempters. Suicide Life Threat Behav. 2001;32(suppl 1):30-41.
12. Busch KA, Fawcett J, Jacobs DG. Clinical correlates of inpatient suicide. J Clin Psychiatry. 2003;64:14-19.
13. Barratt ES, Patton JH. Impulsivity: cognitive, behavioral, and psychophysiological correlates. In: Zuckerman M, ed. Biological Basis of Sensation-Seeking, Impulsivity, and Anxiety. Hillsdale, NJ: Lawrence Erlbaum Associates; 1983:77-116.
14. Peterson LG, Peterson M, O'Shanick G, Swann AC. Violent suicide attempts: lethality of method vs intent. Am J Psychiatry. 1985;142:228-231.
15. Goodman LA, Salyers MP, Mueser KT, et al. Recent victimization in women and men with severe mental illness: prevalence and correlates. J Trauma Stress. 2001; 14:615-632.
16. Simon TR, Anderso M, Thompson MP, et al. Assault victimization and suicidal ideation or behavior within a national sample of US adults. Suicide Life Threat Behav. 2002;32:42-50.
17. Dilsaver SC, Chen YR, Swann AC, et al. Suicidality in patients with pure and depressive mania. Am J Psychiatry. 1995;151:1312-1315.
18. Swann AC, Stokes PE, Secunda S, et al. Depressive mania vs agitated depression: biogenic amine and hypothalamic-pituitary-adrenocortical function. Biol Psychiatry. 1994;35:803-813.
19. Kotin J, Goodwin FK. Depression during mania: clinical observations and theoretical implications. Am J Psychiatry. 1971;129:55-62.
20. Schweizer E, Dever A, Clary C. Suicide upon recovery from depression. A clinical note. J Nerv Ment Dis. 1988; 176:633-636.
21. Craig TJ, Ye Q, Bromet EJ. Mortality among first- admission patients with psychosis. Compr Psychiatry. 2006;47:246-251.
22. Sachs GS. Bipolar mood disorder: practical strategies for acute and maintenance phase treatment. J Clin Psychopharmacol. 1996;16(suppl 1):32S-47S.
23. Teicher MH, Glod CA, Cole JO. Antidepressant drugs and the emergence of suicidal tendencies. Drug Saf. 1993;8:186-212.
24. Sachs GS, Yan LJ, Swann AC, Allen MH. Integration of suicide prevention into outpatient management of bipolar disorder. J Clin Psychiatry. 2001;62(suppl 25):3-11.
25. Pinto OC, Akiskal HS. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder. J Affective Disord. 1998;51:333-343.
26. Allen MH, Currier GW, Hughes DH, et al. The expert consensus guideline series. Treatment of behavioral emergencies. Postgrad Med. 2001;(spec no):1-88.
27. Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26:42-49.
28. Cure S, Rathbone J, Carpenter S. Droperidol for acute psychosis. Cochrane Database Syst Rev. 2004;4: CD002830.
29. Gerlach J, Larsen EB. Subjective experience and mental side-effects of antipsychotic treatment. Acta Psychiatr Scand Suppl. 1999;395:113-137.
30. Kinghorn WA, McEvoy JP. Aripiprazole: pharmacology, efficacy, safety and tolerability. Expert Rev Neurother. 2005;5:297-307.
31. Ghelber D, Belmaker RH. Tardive dyskinesia with quetiapine. Am J Psychiatry. 1999;156:796-797.
32. Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations. J Clin Psychiatry 1998;59(suppl 12):17-22.
33. Chengappa KN, Levine J, Ulrich R, et al. Impact of risperidone on seclusion and restraint at a state psychiatric hospital. Can J Psychiatry. 2000;45:827-832.
34. Tohen M, Jacobs TG, Grundy SL, et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzapine HGGW Study Group. Arch Gen Psychiatry. 2000;57:841-849.
35. Keck PE Jr, Versiani M, Potkin S, et al. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003;160:741-748.
36. Brook S. A pilot study of intramuscular ziprasidone in the short-term treatment of patients with acute exacerbation of schizophrenia. Hum Psychopharmacol. 2000; 15:521-524.
37. Bowden CL, Grunze H, Mullen J, et al. A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. J Clin Psychiatry. 2005;66: 111-121.
38. Keck PE Jr, Marcus R, Tourkodimitris S, et al. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry. 2003;160:1651-1658.
39. Allen MH, Currier GW, Carpenter D, et al. Treatment of behavioral emergencies 2005. J Psychiatr Pract. 2005; 11(suppl 1):5-108.
40. Altamura AC, Sassella F, Santini A, et al. Intramuscular preparations of antipsychotics: uses and relevance in clinical practice. Drugs. 2003;63:493-512.
41. Chengappa KN, Vasile J, Levine J, et al. Clozapine: its impact on aggressive behavior among patients in a state psychiatric hospital. Schizophr Res. 2002;53:1-6.
42. Buckley P, Bartell J, Donenwirth K, et al. Violence and schizophrenia: clozapine as a specific antiaggressive agent. Bull Am Acad Psychiatry Law. 1995;23:607-611.
43. Volavka J, Czobor P, Nolan K, et al. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or halo-peridol. J Clin Psychopharmacol. 2004;24:225-228.
44. Fehr BS, Ozcan ME, Suppes T. Low doses of cloza-pine may stabilize treatment-resistant bipolar patients. Eur Arch Psychiatry Clin Neurosci. 2005;255:10-14.
45. Swann AC, Bowden CL, Calabrese JR, et al. Pattern of response to divalproex, lithium, or placebo in four naturalistic subtypes of mania. Neuropsychopharmacology. 2002;26:530-536.
46. Hollander E, Tracy KA, Swann AC, et al. Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders. Neuropsychopharmacology. 2003;28:1186-1197.
47. Donovan SJ, Stewart JW, Nunes EV, et al. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Am J Psychiatry. 2000;157:818-820.
48. Steiner H, Petersen ML, Saxena K, et al. Divalproex sodium for the treatment of conduct disorder: a random- ized controlled clinical trial. J Clin Psychiatry. 2003;64: 1183-1191.
49. Vitiello B, Behar D, Hunt J, et al. Subtyping aggression in children and adolescents. J Neuropsychiatry Clin Neurosci. 1990;2:189-192.
50. Kruger S, Braunig P. Intravenous valproic acid in the treatment of severe catatonia. J Neuropsychiatry Clin Neurosci. 2001;13:303-304.
51. McElroy SL, Keck PE, Jr, Stanton SP, et al. A randomized comparison of divalproex oral loading versus haloperidol in the initial treatment of acute psychotic mania. J Clin Psychiatry. 1996;57:142-146.
52. Barratt ES, Stanford MS, Felthous AR, Kent TA. The effects of phenytoin on impulsive and premeditated aggression: a controlled study. J Clin Psychopharmacol. 1997;17:341-349.
53. Chatham-Showalter PE. Carbamazepine for combativeness in acute traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1996;8:96-99.
54. Posey DJ, McDougle CJ. The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive developmental disorders. Harv Rev Psychiatry. 2000;8:45-63.
55. Devarajan S, Dursun SM. Aggression in dementia with lamotrigine treatment. Am J Psychiatry. 2000;157: 1178.
56. Beran RG, Gibson RJ. Aggressive behaviour in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia. 1998;39:280-282.
57. Little JD, Taghavi EH. Disinhibition after lorazepam augmentation of antipsychotic medication. Am J Psychiatry. 1991;148:1099-1100.
58. Ben Porath DD, Taylor SP. The effects of diazepam (valium) and aggressive disposition on human aggression: an experimental investigation. Addict Behav. 2002; 27:167-177.
59. Hollister LE. Interactions between alcohol and benzodiazepines. Recent Dev Alcohol. 1990;8:233-239.
60. Garza-Trevino ES, Hollister LE, Overall JE, Alexander WF. Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. Am J Psychiatry. 1989;146:1598-1601.
61. Janicak PG, Sharma RP, Easton M, et al. A double-blind, placebo-controlled trial of clonidine in the treatment of acute mania. Psychopharmacol Bull. 1989; 25: 243-245.
62. Haspel T. Beta-blockers and the treatment of aggression. Harv Rev Psychiatry. 1995;2:274-281.
63. Pozzi G, Conte G, De Risio S. Combined use of trazodone-naltrexone versus clonidine-naltrexone in rapid withdrawal from methadone treatment. A comparative inpatient study. Drug Alcohol Depend. 2000;59:287-294.
64. Allan ER, Alpert M, Sison CE, et al. Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients. J Clin Psychiatry. 1996;57:455-459.
65. Caspi N, Modai I, Barak P, et al. Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study. Int Clin Psychopharmacol. 2001;16:111-115.
66. Grof P, Grof E. Varieties of lithium benefit. Prog Neuropsychopharmacol Biol Psychiatry. 1990;14:689-696.
67. Fava M. Psychopharmacologic treatment of pathol- ogic aggression.. Psychiatr Clin North Am. 1997;20: 427-451.
68. Frye MA, Calabrese JR, Reed ML, et al. Use of health care services among persons who screen positive for bipolar disorder. Psychiatr Serv. 2005;56:1529-1533.
69. Ernst CL, Bird SA, Goldberg JF, Ghaemi SN. The prescription of psychotropic medications for patients discharged from a psychiatric emergency service. J Clin Psychiatry. 2006;67:720-726.
70. Soltis RP, Cook JC, Gregg AE, Sanders BJ. Interaction of GABA and excitatory amino acids in the basolateral amygdala: role in cardiovascular regulation. J Neurosci. 1997;17:9367-9374.
71. Benes FM. The role of stress and dopamine-GABA interactions in the vulnerability for schizophrenia. J Psychiatr Res. 1997;31:257-275.
72. Juhl RP, Tsuang MT, Perry PJ. Concomitant administration of haloperidol and lithium carbonate in acute mania. Dis Nerv Syst. 1977;38:675-676.
73. Leucht S, McGrath J, White P, Kissling W. Carbamazepine for schizophrenia and schizoaffective psychoses. Cochrane Database Syst Rev. 2002;3:CD001258.
74. Wassef AA, Hafiz NG, Hampton D, Molloy M. Divalproex sodium augmentation of haloperidol in hospitalized patients with schizophrenia: clinical and economic implications. J Clin Psychopharmacol. 2001;21:21-26.
75. Lancee WJ, Gallop R, McCay E, Toner B. The relationship between nurses' limit-setting styles and anger in psychiatric inpatients. Psychiatr Serv. 1995;46:609-613.
76. Melle I, Friis S, Hauff E, et al. The importance of ward atmosphere in inpatient treatment of schizophrenia on short-term units. Psychiatr Serv. 1996;47:721-726.
77. Dilsaver SC, Chen YR, Swann AC, et al. Suicidality, panic disorder, and psychosis in bipolar depression, depressive-mania, and pure mania. Psychiatry Res. 1997; 73:47-56.
78. Coryell W, Leon AC, Turvey C, et al. The significance of psychotic features in manic episodes: a report from the NIMH collaborative study. J Affect Disord. 2001;67: 79-88.
79. Schatzberg AF, Rothschild AJ. Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? Am J Psychiatry. 1992;149:733-745.
80. Smith KM, Larive LL, Romanelli F. Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and g-hydroxybutyrate. Am J Health Syst Pharm. 2002;59:1067-1076.
81. Fergusson DM, Horwood LJ, Swain-Campbell NR. Cannabis dependence and psychotic symptoms in young people. Psychol Med. 2003;33:15-21.
82. Freedman R, Schwab PJ. Paranoid symptoms in patients on a general hospital psychiatric unit. Implications for diagnosis and treatment. Arch Gen Psychiatry. 1978; 35:387-390.
83. Dalton EJ, Cate-Carter TD, Mundo E. Suicide risk in bipolar patients: the role of co-morbid substance use disorders. Bipolar Disord. 2003;5:58-61.
84. Links PS, Heslegrave RJ, Mitton JE, et al. Borderline personality disorder and substance abuse: consequences of comorbidity. Can J Psychiatry. 1995;40:9-14.
85. Beck AT, Steer RA, Trexler LD. Alcohol abuse and eventual suicide: a 5- to 10-year prospective study of alcohol-abusing suicide attempters. J Stud Alcohol. 1989; 50:202-209.
86. Fishbein DH, Herman-Stahl M, Eldreth D, et al. Mediators of the stress-substance-use relationship in urban male adolescents. Prev Sci. 2006;7:113-126.
87. Sher L, Oquendo MA, Galfalvy HC, et al. The relationship of aggression to suicidal behavior in depressed patients with a history of alcoholism. Addict Behav. 2005; 30:1144-1153.
88. King EA, Baldwin DS, Sinclair JM, et al. The Wessex Recent In-Patient Suicide Study, 1. Case-control study of 234 recently discharged psychiatric patient suicides. Br J Psychiatry. 2001;178:531-536.
89. Beck AT, Brown G, Berchick RJ, et al. Relationship between hopelessness and ultimate suicide: a replication with psychiatric outpatients. Am J Psychiatry. 1990;147: 190-195.
90. Beck AT, Brown GK, Steer RA, et al. Suicide ideation at its worst point: a predictor of eventual suicide in psychiatric outpatients. Suicide Life Threat Behav. 1999;29: 1-9.
91. Brent DA, Oquendo M, Birmaher B, et al. Familial pathways to early-onset suicide attempt: risk for suicidal behavior in offspring of mood-disordered suicide attempters. Arch Gen Psychiatry. 2002;59:801-807.
92. Scocco P, Marietta P, Tonietto M, et al. The role of psychopathology and suicidal intention in predicting suicide risk: a longitudinal study. Psychopathology. 2000;33: 143-150.
93. Koller G, Preuss UW, Bottlender M, et al. Impulsivity and aggression as predictors of suicide attempts in alcoholics. Eur Arch Psychiatry Clin Neurosci. 2002;252: 155-160.
94. Stanniland C, Taylor D. Tolerability of atypical antipsychotics. Drug Saf. 2000;22:195-214.