Psychotic symptoms in bipolar disorder and their impact on the illness: A systematic review

Table 1 Prevalence of psychosis in bipolar disorder

Study groups	Lifetime rates	Current rates
BD	n = 40, mean 57%; Median 56%; Range: 17%-93%	n = 32, mean 46%; Median 44%; Range: 11%-99%
BD I	n = 32, mean 61%; Median 64%; Range: 30%-90%	n = 10, mean 43%; Median 40%; Range: 12%-75%
BD II	n = 12, mean 22%; Median 20%; Range: 1%-49%	n = 6, mean 19%; Median 18%; Range: 9%-29%
Mania	BD-n = 5, mean 43%; Median 48%; Range: 19%-63%	BD-n = 201, mean 60%; Median 58%; Range: 25%-90%
	BP I-n = 4, mean 60%; Median 56%; Range: 44%-86%	BP I-n = 51, mean 56%; Median 56%; Range: 8%-91%
Bipolar depression	BD-n = 10, mean 21%; Median 19%; Range: 8%-42%	BD-n = 242, mean 24%; Median 19%; Range: 10%-80%
	BP I-n = 11, mean 27%; Median 27%; Range: 6%-55%	BP I-n = 12, mean 18%; Median 19%; Range: 3%-28%
	BP II-n = 6, mean 15%; Median 10%; Range: 7%-30%	BP II-n = 11, mean 11%; Median 8%; Range: 5%-28%
Mixed episodes	BD-n = 2, mean 50%; Median 50%; Range: 34%-66%	BD-n = 14, mean 47%; Median 40%; Range: 8%-97%
	BP I-n = 3, mean 43%; Median 33%; Range: 10%-86%	BP I-n = 143, mean 52%; Median 50%; Range: 15%-89%
		BP II-n = 2, mean 11%; Median 11%; Range: 7%-15%

¹After excluding outliers, mean and median = 51%.

²After excluding outliers, mean = 19% and median = 18%.

³After excluding outliers, mean = 41% and median = 40%.

Complete details in Supplementary Table 3. BD: Bipolar disorder; BP I: Bipolar disorder type I; BP II: Bipolar disorder type II.

Table 2 Rates of different psychotic symptoms in bipolar disorder

Study groups	Delusions	Hallucinations	First-rank symptoms	Mood congruent symptoms	Mood incongruent symptoms
Lifetime BD (n = 6-16)	Mean = 69%; Median = 71%; Range: 29%-100%	Mean = 37%; Median = 32%; Range: 13%-100%	Mean = 17%; Median = 11%; Range: 4%-44%	Mean = 49%; Median = 47%; Range: 18%-90%	Mean = 37%; Median = 40%; Range: 3%-76%
Lifetime BP I (n = 4-8)	Mean = 55%; Median = 71%; Range: 25%-82%	Mean = 32%; Median = 32%; Range: 23%-43%	Mean = 22%; Median = 25%; Range: 1%-38%	Mean = 37%; Median = 34%; Range: 11%-70%	Mean = 36%; Median = 30%; Range: 19%-66%
Lifetime BP II (n = 0-1)	Mean = 4%; Median = 4%; Range: 4%	Mean = 1%; Median = 1%; Range: 1%	-	-	-
Current BD (n = 2-13)	Mean = 54%; Median = 49%; Range: 16%-99%	Mean = 26%; Median = 19%; Range: 10%-58%	Mean = 26%; Median = 24%; Range: 5%-49%	Mean = 39%; Median = 39% Range: 24%-35%	Mean = 42%; Median = 46%; Range: 8%-75%
Current BP I (n = 1)	-	-	-	Mean = 68%; Median = 68%; Range: 68%	Mean = 32%; Median = 32%; Range: 32%
Current BP II	-	-	-	-	-
Lifetime mania (n = 1-5)	BD and BP I Mean = 77%; Median = 77%; Range: 33%-98%	BD and BP I Mean = 83%; Median = 83%; Range: 55%-100%	Only BP I Mean = 45%; Median = 45%; Range: 34%-59%	Only BD Mean = 87%; Median = 87%; Range: 87%	Only BP I Mean = 74%; Median = 74% Range: 74%
Current mania (n = 8-25)	BD and BP I Mean = 57%; Median = 62%; Range: 11%-87%	BD and BP I Mean = 35%; Median = 41%; Range: 10%-55%	BD and BP I Mean = 28%; Median = 32%; Range: 6%-48%	BD and BP I Mean = 41%; Median = 36%; Range: 20%-87%	BD and BP I Mean = 34%; Median = 36%; Range: 9%-64%
Lifetime bipolar depression (n = 1-3)	BD and BP I Mean = 16%; Median = 16%; Range: 10%-20%	BD and BP I Mean = 25%; Median = 25%; Range: 4%-73%	Only BP I Mean = 18%; Median = 18%; Range: 18%	Only BD Mean = 100%; Median = 100%; Range: 100%	-
Current bipolar depression (n = 2-13)1	BD and BP I Mean = 28%; Median = 22%; Range: 6%-97%	BD and BP I Mean = 14%; Median = 9%; Range: 7%-73%	Only BD Mean = 14%; Median = 14%; Range: 8%-20%	BD and BP I Mean = 54%; Median = 54%; Range: 7%-100%	BD and BP I Mean = 7%; Median = 6%; Range: 0-32%
Lifetime mixed episodes (n = 0-3)	Only BD Mean = 66%; Median = 66%; Range: 33%-100%	Only BD Mean = 55%; Median = 55%; Range: 10%-100%	-	BD and BP I Mean = 64%; Median = 64%; Range: 28%-100%	Only BP I Mean = 72%; Median = 72%; Range: 72%
Current mixed episodes (n = 2- 8)	BD and BP I Mean = 55%; Median = 53%; Range: 19%-90%	BD and BP I Mean = 38%; Median = 38%; Range: 23%-67%	Only BP I Mean = 32%; Median = 32%; Range: 16%-49%	BD and BP I Mean = 27%; Median = 28%; Range: 14%-37%	BD and BP I Mean = 41%; Median = 39%; Range: 22%-63%

¹Lifetime rates of hallucinations in bipolar disorder type II: Mean = 17%, median = 17%, range: 13%-21%. Complete details in Supplementary Table 4. BD: Bipolar disorder; BP I: Bipolar disorder type I; BP II: Bipolar disorder type II.

Table 3 Types of delusions in bipolar disorder

Delusions	Grandiose	Referential	Persecutory	Erotomanic	Jealousy	Somatic	Depressive	Religious
Lifetime BD and BP I (n = 11)	Mean (n = 7) 52%; Median 61%; Range: 24%-69%	Mean (n = 3) 59%; Median 61%; Range: 54%-62%	Mean (n = 9) 40%; Median 40%; Range: 16%-56%	-	Mean (n = 2) 8%; Median 8%; Range: 3%-13%	-	Mean (n = 2) 13%; Median 13%; Range: 12%-15%	Mean (n = 1) 35%; Median 35%; Range: 35%
Current BD (n = 9)	Mean (n = 9) 36%; Median 39%; Range: 4%-75%	Mean (n = 3) 42%; Median 5%; Range: 5%-75%	Mean (n = 8) 35%; Median 30%; Range: 7%-71%	Mean (n = 2) 4%; Median 4%; Range: 4%	-	Mean (n = 3) 16%; Median 11%; Range: 7%-31%	Mean (n = 7) 9%; Median 6%; Range: 3%-36%	Mean (n = 2) 5%; Median 5%; Range: 5%
Lifetime mania (N = 3)	Mean (n = 3) 66%; Median 69%; Range: 41%-88%	-	Mean (n = 3) 21%; Median 21%; Range: 12%-30%	-	Mean (n = 1) 2%; Median 2%; Range: 2%	Mean (n = 2) 16%; Median 16%; Range: 16%	Mean (n = 2) 10%; Median 7%; Range: 7%-13%	Mean (n =1) 3%; Median 3%; Range: 3%
Current mania (n = 23)	Mean (n = 17) 57%; Median 59%; Range: 20%-80%	Mean (n = 7) 43%; Median 41%; Range: 14%-69%	Mean (n = 20) 46%; Median 47%; Range: 8%-90%	Mean (n = 4) 29%; Median 24%; Range: 9%-61%	Mean (n = 1) 3%; Median 3%; Range: 3%	Mean (n = 5) 15%; Median 13%; Range: 1%-35%	Mean (n = 3) 10%; Median 10%; Range: 6%-14%	Mean (n = 7) 27%; Median 27%; Range: 22%-31%
Lifetime depression (n = 2)	-	-	Mean (n = 2) 17%; Median 17%; Range: 15%-20	-	-	-	-	-
Current depression (n = 5)	-	Mean (n = 2) 32%; Median 32%; Range: 32%-33%	Mean (n = 4) 37%; Median 39%; Range: 1%-7%	-	Mean (n = 1) 20%; Median 20%; Range: 20%	Mean (n = 1) 17%; Median 17%; Range: 17%	Mean (n = 3) 12%; Median 7%; Range: 3%-30%	-
Lifetime mixed (n = 1)	-	-	Mean (n = 1) 33%; Median 33%; Range: 33%	-	Mean (n = 1) 33%; Median 33%; Range: 33%	-	-	-
Current mixed (n = 4)	Mean (n = 3) 42%; Median 41%; Range: 19%-66%	Mean (n = 2) 71%; Median 71%; Range: 56%-86%	Mean (n = 4) 46%; Median 31%; Range: 16%-90%	-	-	Mean (n = 3) 7%; Median 10%; Range: 7%-13%	Mean (n = 2) 19%; Median 19%; Range: 6%-33%	-
Overall rates	Mean (n = 39) 51%; Median 54%; Range: 4%-88%	Mean (n = 17) 49%; Median 42%; Range: 5%-86%	Mean (n = 52) 34%; Median 32%; Range: 1%-90%	Mean (n = 6) 16%; Median 14%; Range: 4%-61%	Mean (n = 6) 13%; Median 13%; Range: 3%-33%	Mean (n = 14) 14%; Median 13%; Range: 1%-35%	Mean (n = 19) 12%; Median 10%; Range: 3%-36%	Mean (n = 11)18%; Median 17%; Range: 3%-42%

Complete details in Supplementary Table 5. BD: Bipolar disorder; BP I: Bipolar disorder type I; BP II: Bipolar disorder type II.

Table 4 Types of hallucinations in bipolar disorder

Hallucinations	Auditory/AVH	Visual	Tactile	Olfactory	Gustatory	Somatic	Others
Lifetime BD and BP I (n = 13)	Mean (n = 13) 26%; Median 24%; Range: 3%-52%	Mean (n = 10) 23%; Median 23%; Range: 9%-47%	Mean (n = 1) 16%; Median 16%; Range: 16%	-	-	-	Mean (n = 3) Median 12%; 9%; Range: 3%-13%
Current BD (n = 3)	Mean (n = 3) 17%; Median 17%; Range: 8%-17%	Mean (n = 2) 6%; Median 6%; Range: 3%-9%	Mean (n = 1) 0.3%; Median 0.3%; Range: 0.3%	Mean (n = 2) 1%; Median 1%; Range: 1%	Mean (n = 2) 1%; Median 1%; Range: 1%	Mean (n = 2) 2%; Median 2%; Range: 0.4%-3%	-
Lifetime mania (n = 3)	Mean (n = 3) 40%; Median 39%; Range: 22%-52%	Mean (n = 1) 25%; Median 25%; Range: 25%	-	-	-	Mean (n = 1) 11%; Median 11%; Range: 11%	-
Current mania (n = 18)	Mean (n = 17) 33%; Median 41%; Range: 12%-57%	Mean (n = 8) 20%; Median 17%; Range: 2%-61%	Mean (n =2) 4%; Median 4%; Range: 3%-5%	Mean (n = 2) 8%; Median 8%; Range: 6%-13%	-	Mean (n = 2) 11%; Median 11%; Range: 1%-21%	Mean (n = 5) 27%; Median 28%; Range: 7%-46%
Lifetime depression (n = 2)	Mean (n = 2) 40%; Median 40%; Range: 13%-67%	Mean (n = 1) 7%; Median 7%; Range: 7%	-	-	-	-	Mean (n = 2) 18%; Median 18%; Range: 4%-33%
Current depression (n = 6)	Mean (n = 6) 16%; Median 9%; Range: 4%-50%	Mean (n = 3) 5%; Median 3%; Range: 1%-11%	-	Mean (n = 1) 0.5%; Median 0.5%; Range: 0.5%	Mean (n = 1) 0.5%; Median 0.5%; Range: 0.5%	-	Mean (n = 1) 2%; Median 2%; Range: 2%
Lifetime mixed (n = 1)	Mean (n = 1) 33%; Median 33%; Range: 33%	-	-	-	-	-	-
Current mixed (n = 3)	Mean (n = 3) 37%; Median 41%; Range: 4%-67%	Mean (n = 3) 13%; Median 18%; Range: 2%-20%	Mean (n = 1) 5%; Median 5%; Range: 5%	-	Mean (n = 1) 0.5%; Median 0.5%; Range: 0.5%	Mean (n = 1) 2%; Median 2%; Range: 2%	Mean (n = 1) 6%; Median 6%; Range: 6%
Overall rates	Mean (n = 48) 30%; Median 30%; Range: 3%-67%	Mean (n = 28) 14%; Median 13%; Range: 3%-47%	Mean (n = 1) 6%; Median 6%; Range: 0.3%- 16%	Mean (n = 5) 3%; Median 3%; Range: 1%- 16%	Mean (n = 4) 1%; Median 1%; Range: 0.5%-1%	Mean (n = 5) 8%; Median 8%; Range: 0.4%- 47%	Mean (n = 10) 12%; Median 1%; Range: 1%- 46%

Complete details in Supplementary Table 6. AVH: Auditory verbal hallucinations or hearing voices; BD: Bipolar disorder; BP I: Bipolar disorder type I; BP II: Bipolar disorder type II.

Table 5 Types of first rank symptoms in bipolar disorder

Study groups	Passivity/control	Delusional perception	Somatic passivity	Thought broadcast	Thought insertion	Thought withdrawal	Running commentary	Two or more voices conversing	Thought echo
Lifetime BD and BP I (n = 9)	Mean (n = 4) 10%; Median 11%; Range: 4%-16%	Mean (n = 1) 20%; Median 20%; Range: 20%	-	Mean (n = 3) 11%; Median 14%; Range: 3%-17%	Mean (n = 1) 20%; Median 20%; Range: 20%	Mean (n = 1) 4%; Median 4%; Range: 4%	Mean (n = 4) 17%; Median 17%; Range: 10%-27%	Mean (n = 4) 16%; Median 17%; Range: 5%-27%	Mean (n = 1) 13%; Median 13%; Range: 13%
Current BD (n = 4)	Mean (n = 2) 36%; Median 36%; Range: 18%-49%	Mean (n = 2) 6%; Median 6%; Range: 2%-10%	Mean (n = 1) 7%; Median 7%; Range: 7%	Mean (n = 3) 14%; Median 5%; Range: 5%-18%	Mean (n = 1) 5%; Median 5%; Range: 5%	Mean (n = 1) 2%; Median 2%; Range: 2%	Mean (n = 2) 20%; Median 20%; Range: 4%-37%	Mean (n = 2)12%; Median 12%; Range: 4%-20%	Mean (n = 1) 4%; Median 4%; Range: 4%
Lifetime mania (n = 2)	Mean (n = 2) 27%; Median 27%; Range: 3%-52%	-	-	Mean (n = 1) 6%; Median 6%; Range: 6%	Mean (n = 1) 4%; Median 4%; Range: 4%	Mean (n = 1) 3%; Median 3%; Range: 3%	Mean (n = 1) 1%; Median 1%; Range: 1%	Mean (n = 1) 1%; Median 1%; Range: 1%	Mean (n = 2) 14%; Median 14%; Range: 14%-15%
Current mania (n = 8)	Mean (n = 8) 23%; Median 20%; Range: 5%-48%	-	-	Mean (n = 5) 12%; Median 14%; Range: 2%-21%	Mean (n = 3) 9%; Median 7%; Range: 1%-18%	Mean (n = 3) 9%; Median 3%; Range: 3%-13%	Mean (n = 3) 9%; Median 3%; Range: 2%-14%	Mean (n = 3) 5%; Median 3%; Range: 2%-6%	Mean (n = 3) 5%; Median 2%; Range: 1%-12%
Lifetime depression (n = 1)	Mean (n = 1) 1%; Median 1%; Range: 1%	-	-	Mean (n = 1) 1%; Median 1%; Range: 1%	Mean (n = 1) 1%; Median 1%; Range: 1%	Mean (n = 1) 4%; Median 4%; Range: 4%	-	-	Mean (n = 1) 10%; Median 10%; Range: 10%
Current depression (n = 1)	-	-	-	-	-	-	-	Mean (n = 1) 17%; Median 17%	-
Current mixed (n = 1)	Mean (n = 1) 49%; Median 49%; Range: 49%	-		-	-	-	-	-	-
Overall rates	Mean (n = 18) 24%; Median 24%; Range: 1%-49%	Mean (n = 3) 13%; Median 13%; Range: 2%-20%	Mean (n = 1) 7%; Median 7%; Range: 7%	Mean (n = 17) 9%; Median 8%; Range: 1%-18%	Mean (n = 7) 8%; Median 7%; Range: 1%-20%	Mean (n = 7) 4%; Median 3%; Range: 2%-13%	Mean (n = 10) 12%; Median 10%; Range: 1%-20%	Mean (n = 11) 10%; Median 10%; Range: 1%-27%	Mean (n = 8) 9%; Median 9%; Range: 4%-15%

Complete details in Supplementary Table 7. BD: Bipolar disorder; BP I: Bipolar disorder type I; BP II: Bipolar disorder type II.

Table 6 Demographic and clinical correlates of psychosis in bipolar disorder

Correlates	Studies showing positive association with psychosis	Studies showing inverse association or no association with psychosis1
Younger age	n = 14	n = 48
Female sex	n = 16	n = 51
Single status	n = 11	n = 14
Lower educational levels	n = 9	n = 26
Low income or unemployment	n = 6	n = 14
Ethnic minority status	n = 4	n = 10
Severity of psychotic symptoms in bipolar disorder
Studies showing that psychotic symptoms are less severe in bipolar disorder	Studies showing that psychotic symptoms are more severe in bipolar disorder
n = 20	n = 20
Severity of illness/mood symptoms in psychotic bipolar disorder
Studies showing that the illness/mood symptoms are not more severe in psychotic bipolar disorder	Studies showing that severity of illness/mood symptoms is greater in psychotic bipolar disorder
n = 16	n = 34
Insight and psychotic symptoms in bipolar disorder
Studies showing that psychosis is associated with lack of insight in bipolar disorder	Studies showing that psychosis is not associated with lack of insight in bipolar disorder
n = 15	n = 9
Agitation, aggression and anxiety in psychotic bipolar disorder
Studies showing that agitation, aggression and anxiety are associated with psychosis in bipolar disorder	Studies showing that agitation, aggression and anxiety are not associated with psychosis in bipolar disorder
n = 13	n = 2
Comorbidity and psychotic symptoms in bipolar disorder
Studies showing that psychosis associated with greater comorbidity in bipolar disorder	Studies showing that psychosis is not associated with greater comorbidity in bipolar disorder
n = 21	n = 27

¹Twenty-seven studies found no significant relationships between psychotic bipolar disorder and any of the demographic characteristics. Complete details in Supplementary Tables 8 and 9.

Table 7 Impact of psychotic symptoms on the course and outcome of bipolar disorder

Outcome measure	Studies with positive association with psychosis in bipolar disorder	Studies with negative or no association with psychosis in bipolar disorder
Poor overall outcome	n = 38	n = 39
Earlier age of onset	n = 30	n = 36
Persistent or chronic course of illness	n = 23	n = 18
Lack of remission or lack of recovery	n = 12	n = 15
More frequent relapses or recurrences	n =5	n = 5
Greater number of mood episodes	n = 13	n = 19
Lower proportion with rapid cycling	n = 6	n = 6
Longer duration of illness	n = 5	n = 23
Manic polarity of illness	n = 9	n = 6
Seasonal pattern of illness	n = 2	n = 2
More frequent hospitalizations or longer hospital stays	n =26	n = 15
Poor functioning, poor quality of life, or poor functional outcome	n = 45	n = 46
More frequent suicidal attempts or heightened suicidal behavior	n = 14	n = 35
Good response to lithium treatment	n = 5	n = 10
Switch to diagnosis of bipolar disorder	n = 10	-
Poorer outcome with mood-incongruent psychotic symptoms	n = 21	n = 13
Poorer outcome with first-rank symptoms	n = 3	n = 9

Complete details in Supplementary Table 10.