Table 1.
Demographic and clinical data of suspected psychiatric adverse events with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs)
| Crizotinib No. of cases (%) |
Alectinib No. of cases (%) |
Brigatinib No. of cases (%) |
Ceritinib No. of cases (%) |
Lorlatinib No. of cases (%) |
ALK inhibitors No. of cases (%) |
ALK inhibitors No. of non-cases (%) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total reports# | 29 (0.3) | 18 (0.7) | 10 (1.2) | 12 (0.6) | 26 (2.8) | 95 (0.7) | 14,228 (99.3) | |||||
| Sex | ||||||||||||
|
Females Males Missing |
19 (65.5) 10 (34.5) – |
13 (72.2) 5 (27.8) – |
7 (77.8) 2 (22.2) 1 (–) |
8 (66.7) 4 (33.3) – |
14 (56.0) 11 (44.0) 1 (–) |
61 (65.6) 32 (34.4) 2 (–) |
7,245 (55.9) 5,716 (44.1) 1267 (–) |
|||||
| Age distribution (years) | ||||||||||||
| Adult | 20 (69.0) | 11 (91.7) | 2 (66.7) | 5 (71.4) | 13 (59.1) | 51 (69.9) | 5,745 (55.6) | |||||
|
18–29 30–49 50–64 |
– 6 (30.0) 14 (70.0) |
– 7 (63.3) 4 (36.4) |
– – 2 (100.0) |
1 (20.0) 1 (20.0) 3 (60.0) |
2 (15.4) 6 (46.2) 5 (38.5) |
3 (5.9) 20 (39.2) 28 (54.9) |
246 (4.3) 1937 (33.7) 3562 (62.0) |
|||||
| Elderly | 9 (21.0) | 1 (8.3) | 1 (33.3) | 2 (28.6) | 9 (40.9) | 22 (30.1) | 4250 (41.2) | |||||
|
65–74 75–84 ≥ 85 |
5 (55.6) 4 (44.4) – |
1 (100.0) – – |
– 1 (100.0) – |
1 (50.0) – 1 (50.0) |
6 (66.7) 2 (22.2) 1 (11.1) |
13 (59.1) 7 (31.8) 2 (9.1) |
2571 (60.5) 1401 (33.0) 278 (6.5) |
|||||
| Other | – | – | – | – | – | – | 330 (3.2) | |||||
| Missing | – | 6 (–) | 7 (–) | 5 (–) | 4 (–) | 22 (–) | 3903 (–) | |||||
| Type of reporter | ||||||||||||
|
Consumer Physician Other Missing |
6 (20.7) 10 (34.5) 13 (44.8) – |
10 (55.6) 6 (33.3) 2 (11.1) – |
8 (80.0) 2 (20.0) – – |
3 (25.0) 8 (66.7) 1 (8.3) – |
3 (11.5) 13 (50.0) 10 (38.5) – |
30 (36.4) 39 (43.9) 26 (19.7) – |
4,231 (30.2) 5,616 (40.1) 4,148 (40.2) 233 (–) |
|||||
| Reporter country | ||||||||||||
|
North America Europe Asia Other Missing |
16 (55.2) 5 (17.2) 8 (27.6) – – |
10 (55.6) 7 (38.9) 1 (5.6) – – |
10 (100.0) – – – – |
5 (41.7) 3 (25.0) 4 (33.3) – – |
8 (30.8) 8 (30.8) 10 (38.5) – – |
49 (51.6) 23 (24.2) 23 (24.2) – – |
8,140 (57.2) 2,576 (18.1) 2,980 (21.0) 527 (3.7) 5 (–) |
|||||
| Time to onset (days) | ||||||||||||
| Median (IQR) [no. of cases with available data] | 115 (17–258) [10] | 25 (8–70) [5] | – [0] | 1076 [1] | 5 (3–15) [7] | 19 (7–230) [23] | NC | |||||
| Outcome | ||||||||||||
|
Serious Death/life-threat Disability Hospitalization Other serious Non-serious i.e., missing |
17 (58.6) 5 (17.2) – 6 (20.7) 6 (20.7) 12 (41.4) |
12 (66.7) 1 (5.6) – 10 (55.6) 1 (5.6) 6 (33.3) |
8 (80.0) – – 3 (30.0) 5 (50.0) 2 (20.0) |
10 (83.3) 3 (25.0) – 2 (16.7) 5 (41.7) 2 (16.7) |
23 (88.5) 1 (3.8) 2 (7.7) 9 (34.6) 11 (42.3) 3 (11.5) |
70 (73.7) 10 (10.5) 2 (2.1) 30 (31.6) 28 (29.5) 25 (26.3) |
10,272 (72.2) 3921 (27.6) 121 (0.8) 2875 (20.2) 3355 (23.6) 3956 (27.8) |
|||||
| Action and recovery | ||||||||||||
|
Discontinuation Dechallenge Rechallenge |
7 (24.1) 3 (10.3) – |
4 (22.2) 2 (11.1) – |
– – – |
2 (16.7) 1 (8.3) – |
17 (65.4) 13 (50.0) 1 (3.8) |
30 (31.6) 19 (20.0) 1 (1.1) |
NC NC NC |
|||||
| Synergies or alternative explanations | ||||||||||||
|
Glucocorticoids Brain involvement |
3 (10.3) – |
2 (11.1) 1 (5.6) |
2 (20.0) 3 (30.0) |
– – |
4 (15.4) 1 (3.8) |
11 (11.6) 5 (5.3) |
NC NC |
|||||
| Causality score | ||||||||||||
|
Highly probable Probable Possible Unlikely |
3 (10.3) 23 (79.3) 3 (10.3) – |
1 (5.6) 15 (83.3) 1 (5.6) 1 (5.6) |
– 5 (50.0) 5 (50.0) – |
1 (8.3) 11 (91.7) – – |
10 (38.5) 12 (46.2) 3 (11.5) 1 (3.8) |
15 (15.8) 66 (69.5) 12 (12.6) 2 (2.1) |
NC NC NC NC |
|||||
#In this row, parentheses show the reporting proportion (no. of cases/no. of non-cases concerning the investigated drug); NC: not calculated