Transcript Serotonin syndrome - Exeter Headache Clinic

Serotonin syndrome
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Sternbach Criteria for Serotonin Syndrome
Recent addition or increase in a known serotonergic agent
Absence of other possible etiologies (eg, infection, substance
abuse, withdrawal, etc)
No recent addition or increase of a neuroleptic agent
At least 3 of the following symptoms: Mental status changes
(confusion, hypomania), agitation, myoclonus, hyperreflexia,
diaphoresis, shivering, tremor, diarrhea, incoordination, or fever
29 cases reported to the FDA between 1998 and 2002 of possible
serotonin syndrome in patients taking triptan combined with SSRI
or SNRI reading to FDA warning.
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Shapiro and Tepper (2007)-extrapolating from numbers recorded
by a pharmacy benefit management company determined one
million patient month exposures of triptan SSRI combination.
Assuming 10 times as many cases as reported annual incidence of
serotonin syndrome is less than .03%. No published reports in
patients taking triptan is alone. Postmarketing study or
subcutaneous triptan included 1784 patients on SSRI with no
adverse events. Shapiro R , Tepper SJ; The Serotonin Syndrome, Triptans, and
the Potential for Drug–Drug Interactions. HEADACHE 47; 266–269.
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Serotonin syndrome mediated at 5HT
agonist at 5HT1B 5HT1D.
2A
receptor yet triptan is
Gillman PK. Triptans, serotonin agonists, and serotonin
syndrome (serotonin toxicity): A review. Headache. 2010;50:264-272.
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2007-08 1.3 million prescriptions triptan and SSRI/SNRI90%increase from 2004-05.Of patients taking triptans 21 % are
also taking SSRIs.The number of GPs prescribing has halved yet
number of neurologisyts prescribing has doubled. Sclar D et al. Concomitant
Use of Triptan, and SSRI or SNRI After the US Food and Drug Administration Alert on Serotonin
Syndrome. HEADACHE: 52: 198–203
Mixing Triptans
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156 members of the AHS responded to a survey on
prescribing habits.Of the respondents 2/3 sometoimes
combine injectable sumatriptan with oral sumatriptan .
30% sometimes advise patients to combine a different
triptan with injectable sumatriptan and 21% do so
routinely.
Rothrock J. et al. Mixing Triptans. Headache 2011; 51: 135-140
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Patients were prescribed an oral triptan other than
sumatriptan (zolmitriptan, rizatriptan, almotriptan,
eletriptan,) and asked to take sumatriptan 6 mg injection
for rescue medication if needed.
200 subjects participated in the study and 184 completed.
89% (164) of completers combined the two drugs at least
once to treat a total of 903 attacks. 72% treated more than
three attacks.
Of the 132 subjects who used a combination on three
occasions 89% were either satisfied or very satisfied, 10%
were either dissatisfied or very dissatisfied
No serious adverse events. Further study is needed
SNOOP4
 Systemic
eg.fever ,wt loss-tumours,meningitis,abscess
 Neurologic
e.g.neurologic deficit,fits
 Onset
after 50
 Onset sudden Vascular events e.g. subarachnoid, cerebral
vasoconstriction
 Progressive
 Precipitated
by Valsalva e.g. Chiari malformation
 Postural aggravation e.g. Low pressure headache
 Papilloedema
Topiramate versus Valproate
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A study comparing TPM with DVP in the real
world
Patients selected had less than 15 headache days
a month and were not on a prophylactic.
Topiramate was titrated up to 75mg b.d. as
tolerated. Valproate was titrated up to 500 b.d.
as tolerated. Krymchantowski A et al.Topiramate vs Divalproex Sodium in
the Preventive Treatment of Migraine: A Prospective “Real-World” Study. HEADACHE.
51; 554–558,
Results
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TPM- 40/69 (58%) of patients had greater than 50% reduction. 10
were lost to follow-up, 10 patients failed to achieve 50%
reduction, 6 stopped because of side-effects and 3 withdrew.
DVP-26/51(51%) of patients had greater than 50% reduction.8
were lost to follow-up, 3 failed to achieve a 50% reduction and 10
stopped due to side-effects and 4 withdrew.
From this group with a 50% reduction in headache:
For TPM 17/40(42.5%) had a greater than 75% reduction in
headache.
For DVP 8/26 (30.7%) had greater than 75% reduction in
headache
For the completers side-effects as follows:
TPM-weight loss 50%, paraesthesiae 48%, cognitive
disturbance 20%.
DVP-weight gain 24%, hair loss 24%, 24%GI upset
Combining Topiramate and Valproate
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TPM increased to 50 mg bd stages. Valproate SR increased
to 1 g nocte in stages.
Patients in either group who achieved greater than 50%
reduction in headache but intolerable side-effects had the
dose of TPM reduced to25/50 and valproate added at a
dose of500 nocte. The valproate group were reduced to 500
nocte and TPM added at 25/50.
TPM.157 pts.126 fu, 59 had 50% reduction but 22 had side
effects
Valproate 102 pts, fu 78, 27 had 50% reduction but 16
had side effects.
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38 patients went to next phase
TPM 17/22 (77.3%) reported a decrease in side-effects but
persistence of improvement .Valproate 10/16(62.5 %)
reported a decrease in side-effects but persistence of
improvement
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New Daily Persistent Headache
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1. Gender: female predominance (gender ratio
range 1.4-2.5:1)
2. Age of onset: younger in women, many 2nd3rd decade
3. Location: bilateral in most
4. Intensity: moderate to severe in most patients
5. Pain duration: constant without pain free time
6. Associated symptoms: migrainous features are
common in almost all studies
7. Recognized triggering event in <50%
New Daily Persistent Headache
 Possible
aetiology-Post infectious,
post surgery, post toxic exposure,
neck hypermobility
 Doxycycline effective in 4 cases of
refractory headache(tnf alpha
inhibitor). Also steroids used
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Rozen T. New Daily Persistent Headache: Clinical Perspective. Headache: 51, 641–
649, April 2011