Project
Submitted to
Ms. Sehar Wajid
Submitted by
Hafiza Sana Idrees
MSPSY-22-08
Anam Zafar
MSPSY-22-09
Ms. Clinical Psychology
Session: 2022-2024
Department of Applied Psychology
University of Sahiwal
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Constipation is secondary to Amitriptyline use as Tryptanol
for migraine twenty-four-year year women.
Article Category: Case Report
Abstract Word Count: 103
Manuscript Word Count: 1996
Number of References: 13
Number of Figures: 04
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Constipation is secondary to Amitriptyline use as Tryptanol for migraine twenty-
four-year year women.
By
Hafiza Sana Idrees
Anam Zafar
Approved By
__________________________
3
Acknowledgment
I bowed before Allah Almighty, the All-Knowing, the All-Present, the Merciful, the Most
Gracious, and the Most Benevolent, who is the One and Only Source of All Knowledge and
Wisdom Given to Mankind and Who Has Bestowed This Work upon Me. It is because of
Almighty Allah and his Prophet Hazrat Muhammad that I was able to do this. I want to convey
my sincere appreciation to everyone who helped finish this project and supported my ongoing
interest and drive to learn. I extend my heartfelt gratitude and sincere thanks to Mis Sahar Wajid,
visiting faculty, and the Department of Psychology for her guidance, help, and cooperation. My
deepest thanks also go to my teacher Mis Sahar Wajid, for being so sympathetic, helpful, and
encouraging throughout my drug report effort.
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DECLARATION
I hereby declare that the contents of the Drug report, “Constipation is secondary to
Amitriptyline use as Tryptanol for migraine twenty-four-year year women” is the
product of my own research drug case report without referring to/acknowledging the
original contribution). Further, it is declared that this work has not been submitted for
any diploma/ degree elsewhere.
Hafiza Sana Idrees
Anam Zafar
5
Table of contents
Sr. No. Title Page No.
01 Abstract 07
02 Introduction 08-12
03 Identifying 13
information
Background of 13
clients problem
with references
Case report 13
04 Discussion 14
05 Conclusion 15
06 References 16-17
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Abstract
Amitriptyline is one of the leading medications used for migraine as tryptanol.
Amitriptyline may cause various side effects ranging from mild symptoms such as
constipation, and dry mouth to severe adverse events such as seizures and coma. We
present the case of a young woman who was started on amitriptyline for migraine but
developed constipation. The patient’s digestive system normalized after stopping
amitriptyline but was disturbed and reintroduced. The case highlights the possibility of
amitriptyline Induced constipation then we recommend regular digestive system
checkups for the patient on amitriptyline regardless of the dose.
Key Words: Amitriptyline, migraine, side effect, constipation, digestive system
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Introduction
Migraine headache is a common type of severe headache associated with
symptoms like nausea, aura, and photophobia. Migraine headaches were once believed to
be due to the alteration of cranial blood vessels' tone, which produces different migraine
manifestations. Most current evidence supports that a primary neuronal dysfunction and
the subsequent intra-cranial and extra-cranial changes are behind the migraine's four
known phases. The pathophysiology includes a cortical spread in trigeminal
vasculaemino-vascular system activation, and increased sensitization of neurons, among
other causes. Migraines can be classified as episodic (less than 15 days/month) and
chronic migraine (more than 15 days/month).
The worldwide prevalence of migraine is around 10%, with higher rates found in
North America, South and Central America, Europe, Asia, and Africa, respectively. In
comparison, a study in Saudi Arabia showed migraine prevalence as high as 26%, with
female predominance.
Acute episodic migraines are treated with non-steroidal anti-inflammatory drugs
(NSAIDs) and triptans, while several lines of prophylaxis are offered for chronic
migraines. Among the first line is amitriptyline, a tricyclic antidepressant (TCA) proven
to be a practical choice to prevent migraines but is less favorable for its side effects
profile than other drugs. Common side effects include but are not limited to tachycardia,
increased appetite, weight gain, urinary retention, dry mouth, blurry vision, and
constipation.
Herein, we describe a case of a young gentleman with a migraine who received
amitriptyline as prophylaxis but developed hypertension and resolved once stopping the
drug.
Figure 1 - Molecular structure of amitriptyline.
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In 1961, amitriptyline was introduced to the US market as a tricyclic
antidepressant (TCA), and it is still prescribed regularly for major depression. It has been
approved in more than 56 countries worldwide and is sold under the brand names
Saroten, Elavil, and Endep, among many others. In 2008, it was the third most frequently
prescribed antidepressant in Germany, at 94 million defined daily doses. In addition to
major depressive disorder, amitriptyline is used to treat other forms of depression,
chronic pain, migraine, anxiety disorders, fibromyalgia, neuropathic pain, interstitial
cystitis, nocturnal enuresis, eating disorders, and post-herpetic neuralgia ( Brueckle et al.,
2020).
Amitriptyline was the second tricyclic antidepressant to be synthesized by Merck
in 1960 after imipramine. Its main action is to increase the activity of serotonergic and
noradrenergic neurons by inhibiting central serotonin and noradrenaline reuptake at the
synapse but has a much lesser effect on dopamine. It exhibits further blockade at
adrenergic (a1), histaminergic (H1), muscarinic (mCh), and NMDA receptor sites, as
well as sodium and L-type calcium channels, leading to many potential unintended and
toxic clinical effects.
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Amitriptyline undergoes extensive first-pass metabolism in the liver through the
cytochrome p450 enzymes CYP2D6 and CYP2C19 to nortriptyline, which has additional
clinical effects. Amitriptyline is more potent at the serotonin receptor, while nortriptyline
has greater action on noradrenaline. Amitriptyline has 45% bioavailability and is tightly
protein bound in plasma. It is largely really excreted in conjugated forms but does not
require dose adjustment in renal impairment.
Drug-drug interaction; when used along with amitriptyline, some drugs may
cause an increase in serotonin concentrations; such drugs include isocarboxazid,
phenelzine, procarbazine, safinamide, selegiline, tranylcypromine, sertraline. These
drugs can cause serotonin syndrome. Drug food interaction; do not drink alcohol.
Dangerous side effects or death can occur when alcohol is combined with amitriptyline.
The mechanism by which anticholinergic medications contribute to long-term
cognitive decline and possibly other neurodegenerative conditions remains elusive, with
postulated mechanisms including cholinergic depletion with loss of
trophic/neuroprotective activity, cerebral vascular dysregulation, and neuroinflammation
(Radu et al., 2017). Evidence also exists for a similar role for muscarinic receptors in the
CNS including findings of M1, M3, and M4 muscarinic receptors as the most abundant
in brain microvascular endothelial cells (Radu et al., 2017). Cholinergic dilation of
cerebral blood vessels in M5 muscarinic acetylcholine receptor knockout mice (Yamada
et al., 2001). In addition, anticholinergic drugs have been shown to induce inflammation
through the proliferation and activation of microglia as well as increasing interleukin-1β
expression in the brains of tau-model mice (Yoshiyama et al., 2012).
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Figure 2 - Pharmacological action of cholinergic neuron
Histamine (an endogenous chemical messenger) induces an increased level of
vascular permeability, which leads to fluid moving from capillaries into the surrounding
tissues. The overall outcome of this is increased swelling and dilation of vessels.
Antihistamines stop this effect by acting as antagonists at the H-1 receptors. The clinical
benefit is a reduction in allergy symptoms and any related symptoms.
First-generation antihistamines easily cross the blood-brain barrier into the central
nervous system and antagonize H-1 receptors, leading to a different therapeutic and
adverse effect profile in contrast to second-generation antihistamines selectively bind to
peripheral histamine receptors. Parietal cells in the gastrointestinal tract secrete
hydrochloric acid. They undergo regulation by acetylcholine, gastrin, and also histamine.
Histamine is released from enterochromaffin-like (ECL) cells. When histamine binds to
the H-2 receptors on parietal cells, cyclic adenosine monophosphate (cAMP) increases,
inducing protein kinase A. This action then leads to phosphorylation of the proteins that
take part in the transport of hydrogen ions. Thus increased histamine leads to increased
stomach acid, e.g., HCl secretion (Farzam et al., 2019)
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Fig 3- Antihistamines mechanism of action
Additionally, there has not been a documented change in mood in studies of
patients achieving an analgesic benefit. The use of amitriptyline is partly limited by
concern over side effects. Sedation is common and it is usually prescribed at night to
avoid this. Anti-muscarinic effects include dry eyes, postural hypotension, glaucoma,
constipation, confusion, and urinary retention. Other potential effects are
hypersensitivity, akathisia, mania, and cardiac arrhythmia. Concerns have been raised
about a small increased risk of suicidal ideation in children and young people treated
with this drug.
Amitriptyline is potentially lethal in overdose, hence its decline in the treatment
of psychiatric disorders. The main concerns are cardiac toxicity through cardiac sodium
channel blockade and serotonin syndrome. There is multiple drugs interact that should be
taken into account when prescribing the drug, particularly with those which augment the
cytochrome P450 system, monoamine oxidase inhibitors, and cisapride (as it can
potentiate QTc prolongation) (Devine, 2016).
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Identifying information
Background of client’s problem with references
One of the previous is in a controlled trial of amitriptyline hydrochloride in
migraine prophylaxis, 100 patients received a placebo for a four-week baseline period
and then were randomized in a double-blind fashion to therapy with amitriptyline (47
subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to
four 25-mg tablets of amitriptyline hydrochloride or an identical placebo per day.
Comparing the first and second four-week periods for each patient, the conditions of
55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were ≥ 50%
improved and the difference between amitriptyline and placebo response rates was
significant (P <.05). Non-depressed subjects with severe migraine and depressed subjects
with less severe migraine responded best to amitriptyline, whereas depressed subjects
with severe migraine had little headache relief. Amitriptyline is an effective anti-
migraine agent and the anti-migraine effect seems relatively independent of
antidepressant activity (Couch & Hassanein, 1979).
According to a previous case study a case of intestinal pseudo-obstruction,
spontaneous caecal perforation, and fecal peritonitis caused by an overdose of
amitriptyline. This rare but serious complication should be borne in mind in patients who
remain constipated while convalescing after self-poisoning with tricyclic antidepressants
(McMahon, 1989).
Case report
Mahnoor is 24 years old. She is the middle of five siblings. Her father works as
an owner at a tea stall, while his mother is a housewife. He belongs to a Punjabi-
speaking middle-class family residing in Sahiwal. The patient was referred by her uncle.
She is medically and surgically healthy and presented with a six-month history of
right-sided throbbing headaches associated with nausea, vomiting, and photophobia
nearly every day. The headache is preceded by 15-30 minutes of blurry vision. Initially,
the pain was relieved by lying down in a dark, quiet room or oral acetaminophen. Later,
the patient required ibuprofen to alleviate the pain as the headache would persist for two
days. Initial examination showed a blood pressure of 123/69 mmHg, a heart rate of 72
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beats per minute, a normal respiratory rate, and a normal digestive system. The
neurological examination was completely unremarkable.
The basic blood tests were within normal limits. The patient was diagnosed with
headaches headache and started on Ibuprofen 400 mg once daily. A month later, the
patient did not feel any improvement; thus, she hatched to amitriptyline 10 mg once
daily. After a month, the dose was increased to 25 mg as there was no improvement. The
patient’s migraine attacks improved to once monthly; however, the patient noticed a new
headache character affecting the head's posterior part, not similar to his previous
migraine three months after starting amitriptyline. There was no past history of altered
bowel habits Serum electrolytes were normal. Apart from urinary retention requiring
temporary catheterization, his recovery over the first week was uneventful. However, he
became constipated and had increasing abdominal distension.
On the eleventh day, he developed bilious vomiting and watery diarrhea but
denied abdominal pain. On examination, the pulse rate was 120/minute, the blood
pressure normal, and the temperature 38°C. The abdomen was grossly distended. The
patient decided to stop amitriptyline and felt betterment in her digestive system, which
normalized after one week. On the next clinic visit, her blood pressure was 111/62
mmHg, said now she has decreasing abdominal distension and the migraine headache
was persistent but responding to analgesics. She was asked to resume amitriptyline to 10
mg and monitor her abdominal distension, then increase the dose to 25 mg if the
migraine was not controlled and abdominal distension did not increase. After one month,
the patient's abdominal distention was normal, but she still complains of migraines, so
she increased the dose to 25 mg as instructed. However, a week later, the patient's
abdominal distension increased, so the patient stopped amitriptyline. After six months,
the patient was not on any medications, and her abdominal distension remained normal.
His migraine attacks were much less frequent and responded to simple analgesics.
Discussion
Amitriptyline has been shown to be effective for the prophylaxis of migraine in
adults. Studies in children have been quite limited. In adults, the suggested effective dose
range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a
dosage range in clinical practice that often varies from a very low dose to a dose
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equivalent to that used in adults. Two hundred seventy-nine children had headaches
occurring frequently enough to indicate prophylactic treatment. A total of 84.2% of the
children reported an overall perception of being better, while 11.6% reported being the
same. The frequency of headaches improved to 9.2 days per month. The average severity
was reduced to 5.1, and the average duration was reduced to 6.3 hours. If daily or
continuous headaches were excluded, the improvements were more marked. It was
concluded as Amitriptyline is an effective prophylactic medication for children with
frequent headaches (Hershey et al., 2000).
One study was conducted on the side effects of Amitriptyline. And it was concluded
that the probability of amitriptyline causes hypertension, even if no other medications
were used simultaneously. Regular follow-up for blood pressure, especially in the early
days of starting amitriptyline, is considered reasonable, even with small doses.
Discontinuing amitriptyline may result in resolving hypertension without the need for
antihypertensive medications. It was actually evidence of our study because this case
study also covers the side effect of constipation due to the overdose of the drug
Amitriptyline (Hmoud et al., 2021).
Conclusion
Previous studies found that doses between 2.5 and 100 mg per day were an effective
treatment for chronic headaches, with approximately 75 percent of patients reporting an
improvement in their symptoms for the treatment of migraine headaches. But if patient
didn’t follow proper instructions, and also starts taking high doses of that drug then I,t
will surely, cause side effects such as hypertension, constipation and dry mouth etc.
Fig 4- Proportion of drug Amitriptyline effectiveness on patients
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References
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Anticholinergics boost the pathological process of neurodegeneration with increased
inflammation in a tauopathy mouse model.
Brueckle, M. S., Thomas, E. T., Seide, S. E., Pilz, M., Gonzalez-Gonzalez, A. I.,
Nguyen, T. S., & Muth, C. (2020). Adverse drug reactions associated with
amitriptyline—protocol for a systematic multiple-indication review and meta-
analysis. Systematic Reviews, 9(1), 1-8.
Cholinergic dilation of cerebral blood vessels (2001) is abolished in
14096–14101.
Couch, J. R., & Hassanein, R. S. (1979). Amitriptyline in migraine prophylaxis.
Archives of Neurology, 36(11), 695-699.
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Marzoughi, S., Banerjee, A., Jutzeler, C. R., Prado, M. A., Rosner, J., Cragg, J. J., &
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Journal of Neurochemistry, 158(6), 1334-1344.
McMahon, A. J. (1989). Amitriptyline overdose is complicated by intestinal pseudo-
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P., McKinzie, D. L., Felder, C. C., Deng, C. X., Faraci, F. M., & Wess, J.
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Hmoud, M., Al-Husayni, F., Alzahrani, A., Alharthi, A., & Alwafi, E. (2021).
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26-year-old man. Cureus, 13(1).
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