Hypertension induced by sudden clozapine withdrawal in a schizophrenia patient with metabolic syndrome: A case report

Table 1 Adverse Drug Reaction Probability Scale

	Yes	No	Do not know	Score
Are there previous conclusive reports on this reaction?	+1	0	0	1
Did the adverse event appear after the suspected drug was administered?	+2	-1	0	2
Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?	+1	0	0	1
Did the adverse reaction reappear when the drug was readministered?	+2	-1	0	2
Are there alternative causes (other than the drug) that could on their own have caused the reaction?	-1	+2	0	0
Did the reaction reappear when a placebo was given?	-1	+1	0	0
Was the drug detected in the blood (or other fluids) in concentrations known to be toxic?	+1	0	0	0
Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?	+1	0	0	1
Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	+1	0	0	0
Was the adverse event confirmed by any objective evidence?	+1	0	0	1
Total score	8

Table 2 Diagnostic criteria for metabolic syndrome

Criterion	Definition	Patient portrait	Yes/no
Abdominal obesity	Waist circumference ≥ 102 cm for men	106 cm	Yes
Hyperglycemia	Fasting plasma glucose ≥ 100 mg/dL or ongoing treatment	Ongoing treatment	Yes
Low HDL-cholesterol	HDL < 40 mg/dL for men or ongoing treatment	39 mg/dL	Yes
Hypertriglyceridemia	Triglycerides ≥ 150 mg/dL or ongoing treatment	145.14 mg/dL	No
Hypertension	Blood pressure ≥ 130/85 mmHg or ongoing treatment	Ongoing treatment	Yes

HDL: High-density lipoprotein.

Table 3 Detailed medication, blood pressure and clinical course after clozapine withdrawal

Days since discontinuation	Antihypertensive dosage	Clozapine restart	Blood pressure readings	Clinical course
1	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	No	140/82 mmHg	No
2	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	No	NA	No
3	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	No	NA	No
4	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	No	NA	No
5	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	No	143/90 mmHg	No
6	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + felodipine sustained-release tablets 5 mg	No	160/90 mmHg	Headache tachycardia
7	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
8	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	166/99 mmHg	Tachycardia
9	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
10	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	165/97 mmHg	No
11	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	170/90 mmHg	Tachycardia
12	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
13	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
14	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
15	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	190/90 mmHg	Headache tachycardia
16	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
17	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	168/110 mmHg	No
18	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	170/100 mmHg	No
19	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg	No	NA	No
20	Nifedipine controlled-release tablets 30 mg + irbesartan tablets 150 mg + nifedipine controlled-release tablets 30 mg	No	181/105 mmHg	Tachycardia
21	Nifedipine controlled-release tablets 60 mg + irbesartan tablets 150 mg	No	187/96 mmHg	No
22	Nifedipine controlled-release tablets 60 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	180/95 mmHg	No
23	Nifedipine controlled-release tablets 60 mg + irbesartan tablets 150 mg	No	NA	No
24	Nifedipine controlled-release tablets 60 mg + irbesartan tablets 150 mg + captopril tablets 25 mg	No	172/87 mmHg	No
25	Nifedipine controlled-release tablets 60 mg + irbesartan tablets 150 mg + nifedipine sustained-release tablets 20 mg	No	186/98 mmHg	No
26	Nifedipine controlled-release tablets 60 mg + captopril tablets 75 mg + metoprolol succinate sustained-release tablets 23.75 mg + nifedipine sustained-release tablets 20 mg	100 mg	180/96 mmHg	Tachycardia
27	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg + nifedipine sustained-release tablets 20 mg	100 mg	175/102 mmHg	Tachycardia
28	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg	100 mg	180/100 mmHg	No
29	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg + nifedipine sustained-release tablets 20 mg	100 mg	179/99 mmHg	No
30	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg	100 mg	176/98 mmHg	No
31	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg	150 mg	174/100 mmHg	No
32	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg	150 mg	174/96 mmHg	No
33	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg	150 mg	173/93 mmHg	No
34	Nifedipine sustained-release tablets 40 mg + captopril tablets 75 mg + metoprolol tartrate tablets 100 mg + nitroglycerin injection 10 mg	150 mg	210/115 mmHg	Headache tachycardia
35	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + metoprolol tartrate tablets 100 mg	200 mg	150/88 mmHg	No
36	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + metoprolol tartrate tablets 100 mg	200 mg	145/94 mmHg	No
37	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + metoprolol tartrate tablets 100 mg	200 mg	183/96 mmHg	Tachycardia
38	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	155/89 mmHg	No
39	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + metoprolol tartrate tablets 100 mg	200 mg	NA	No
40	Nifedipine sustained-release tablets 40 mg + captopril tablets 150 mg + metoprolol tartrate tablets 100 mg + urapidil hydrochloride injection 25 mg	200 mg	186/108 mmHg	Headache tachycardia
41	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	155/90 mmHg	No
42	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	156/94 mmHg	No
43	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	143/92 mmHg	No
44	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	NA	No
45	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	NA	No
46	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	137/79 mmHg	No
47	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	152/94 mmHg	No
48	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	154/94 mmHg	No
49	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	137/88 mmHg	No
50	Nifedipine sustained-release tablets 80 mg + captopril tablets 150 mg + irbesartan tablets 150 mg	200 mg	133/78 mmHg	No
3-month follow-up	Nifedipine sustained-release tablets 80 mg + irbesartan tablets 150 mg	250 mg	115/74 mmHg	No
6-month follow-up	Amlodipine besylate tablets 5 mg + irbesartan tablets 150 mg	225 mg	122/78 mmHg	No

NA: No assessment.