Making sense of medication side-effects
by David Baxter, Psychlinks Blog
April 30, 2005

You’ve just come home from a visit to your doctor with a new prescription. If you are like many people today, one of the first things you will do is read the leaflet your pharmacist gave you and then go to the internet to look for more information. For many people, what they find there can be alarming.

Websites like www.RxList.com include tables of possible side-effects that patients in various research studies may have experienced. Sometimes, this can be quite a long list, but on closer inspection in most cases you will see that no individual side-effect is experienced by the majority of people taking the medication. You should also note that in most cases the information provided will include a group called “Placebo” — a group which is given a “sugar pill” instead of the actual drug — and often patients in this group will also report experiencing those side-effects.

So what does it all mean? How does one read these sometimes frightening data tables to make sense of them?

Read the fine print
Let’s look at a popular drug in the family of newer antidepressant/antianxiety medications: Effexor (venlafaxine). On this page from RxList, you will find tables (Tables 7-10) with possible side-effects listed vertically down the left hand side and data from studies comparing Effexor XR (the extended release version of this medication) to placebo in three different patient groups: Major Depressive Disorder, General Anxiety Disorder, and Social Anxiety Disorder. In this table, virtually all of the listed side-effects are reported as occurring in less than 3% of patients who continued to take the medication over an 8- to 12-week period. However, it is important to note that the data presented in Table 2 are side effects experienced during discontinuation of the drug after taking it for 8 to 12 weeks.

Table 7 : Treatment-Emergent Adverse Event Incidence in Short-Term Placebo-Controlled Effexor XR Clinical Trials in Patients with Major Depressive Disorder1,2

Body System Preferred Term % Reporting Event
~ Effexor XR
(n = 357)
Placebo
(n = 285)
Body as a Whole
Asthenia 8% 7%
Cardiovascular System
Vasodilatation3 4% 2%
Hypertension 4% 1%
Digestive System
Nausea 31% 12%
Constipation 8% 5%
Anorexia 8% 4%
Vomiting 4% 2%
Flatulence 4% 3%
Metabolic/Nutritional
Weight Loss 3% 0%
Nervous System
Dizziness 20% 9%
Somnolence 17% 8%
Insomnia 17% 11%
Dry Mouth 12% 6%
Nervousness 10% 5%
Abnormal Dreams4 7% 2%
Tremor 5% 2%
Depression 3% < 1%
Paresthesia 3% 1%
Libido Decreased 3% < 1%
Agitation 3% 1%
Respiratory System
Pharyngitis 7% 6%
Yawn 3% 0%
Skin
Sweating 14% 3%
Special Senses
Abnormal Vision5 4% < 1%
Urogenital System
Abnormal Ejaculation (male)6,7 16% < 1%
Impotence7 4% < 1%
Anorgasmia (female)8,9 3% < 1%
1Incidence, rounded to the nearest %, for events reported by at least 2% of patients treated with Effexor XR, except the following events which had an incidence equal to or less than placebo: abdominal pain, accidental injury, anxiety, back pain, bronchitis, diarrhea, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, pain, palpitation, rhinitis, and sinusitis.
2 < 1% indicates an incidence greater than zero but less than 1%.
3Mostly “hot flashes.”
4Mostly “vivid dreams,” “nightmares,” and “increased dreaming.”
5Mostly “blurred vision” and “difficulty focusing eyes.”
6Mostly “delayed ejaculation.”
7Incidence is based on the number of male patients.
8 Mostly “delayed orgasm” or “anorgasmia.”
9Incidence is based on the number of female patients.

Table 8 : Treatment-Emergent Adverse Event Incidence in Short-Term Placebo-Controlled Effexor XR Clinical Trials in GAD Patients1,2

Body System Preferred Term % ReportingEvent
~ Effexor XR
(n= 1381)
Placebo
(n =555)
Body as a Whole
Asthenia 12% 8%
Cardiovascular System
Vasodilatation3 4% 2%
Digestive System
Nausea 35% 12%
Constipation 10% 4%
Anorexia 8% 2%
Vomiting 5% 3%
Nervous System
Dizziness 16% 11%
Dry Mouth 16% 6%
Insomnia 15% 10%
Somnolence 14% 8%
Nervousness 6% 4%
Libido Decreased 4% 2%
Tremor 4% < 1%
Abnormal Dreams4 3% 2%
Hypertonia 3% 2%
Paresthesia 2% 1%
Respiratory System
Yawn 3% < 1%
Skin
Sweating 10% 3%
Special Senses
Abnormal Vision5 5% < 1%
Urogenital System
Abnormal Ejaculation6,7 11% < 1%
Impotence 5% < 1%
Orgasmic Dysfunction (female) 8,9 2% 0%
1Adverse events for which the Effexor XR reporting rate was less than or equal to the placebo rate are not included. These events are: abdominal pain, accidental injury, anxiety, back pain, diarrhea, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, myalgia, pain, palpitation, pharyngitis, rhinitis, tinnitus, and urinary frequency.
2 < 1% means greater than zero but less than 1%.
3Mostly “hot flashes.”
4Mostly “vivid dreams,” “nightmares,” and “increased dreaming.”
5Mostly “blurred vision” and “difficulty focusing eyes.”
6Includes “delayed ejaculation” and “anorgasmia.”
7Percentage based on the number of males (Effexor XR = 525, placebo = 220).
8Includes “delayed orgasm,” “abnormal orgasm,” and “anorgasmia.”
9Percentage based on the number of females (Effexor XR = 856, placebo = 335).


Table 9 : Treatment-Emergent Adverse Event Incidence in Short-Term Placebo-Controlled Effexor XR Clinical Trials in Social Anxiety Disorder Patients1,2

Body System Preferred Term % Reporting Event
~ Effexor XR
(n = 819)
Placebo
(n = 695)
Body as a Whole
Headache 38% 34%
Asthenia 19% 9%
Abdominal Pain 6% 4%
Accidental Injury 4% 3%
Cardiovascular System
Hypertension 5% 3%
Vasodilatation3 3% 2%
Palpitation 3% 1%
Digestive System
Nausea 31% 9%
Anorexia4 17% 2%
Constipation 9% 3%
Diarrhea 8% 6%
Dyspepsia 7% 6%
Vomiting 3% 2%
Metabolic/Nutritional
Weight Loss 2% <1%
Nervous System
Insomnia 24% 8%
Somnolence 20% 8%
Dry Mouth 17% 4%
Dizziness 16% 8%
Nervousness 10% 5%
Libido Decreased 8% 2%
Anxiety 5% 4%
Tremor 5% 2%
Agitation 3% 1%
Abnormal Dreams5 3% < 1%
Twitching 3% < 1%
Respiratory System
Yawn 5% < 1%
Skin
Sweating 13% 4%
Special Senses
Abnormal Vision6 4% 2%
Urogenital System
Abnormal Ejaculation7,8 19% < 1%
Impotence8 6% < 1%
Orgasmic Dysfunction9,10 5% < 1%
1Adverse events for which the Effexor XR reporting rate was less than or equal to the placebo rate are not included. These events are: arthralgia, back pain, dysmenorrhea, flu syndrome, infection, pain, pharyngitis, rhinitis, and upper respiratory infection.
2 < 1% means greater than zero but less than 1%.
3Mostly “hot flashes.”
4Mostly “decreased appetite” and “loss of appetite.”
5Mostly “vivid dreams,” “nightmares,” and “increased dreaming.”
6Mostly “blurred vision.”
7Includes “delayed ejaculation” and “anorgasmia.”
8Percentage based on the number of males (Effexor XR = 454, placebo = 357).
9Includes “abnormal orgasm” and “anorgasmia.”
10Percentage based on the number of females (Effexor XR = 365, placebo = 338).

Table 10 : Treatment-Emergent Adverse Event Incidence in Short-Term Placebo-Controlled Effexor XR Clinical Trials in Panic Disorder Patients1,2

Body System Preferred Term Reporting Event
~ Effexor XR
(n= 1001)
Placebo
(n = 662)
Body as a Whole
Asthenia 10% 8%
Cardiovascular System
Hypertension 4% 3%
Vasodilatation3 3% 2%
Digestive System
Nausea 21% 14%
Dry mouth 12% 6%
Constipation 9% 3%
Anorexia4 8% 3%
Nervous System
Insomnia 17% 9%
Somnolence 12% 6%
Dizziness 11% 10%
Tremor 5% 2%
Libido Decreased 4% 2%
Skin
Sweating 10% 2%
Urogenital System
Abnormal Ejaculation5,6 8% < 1%
Impotence6 4% < 1%
Orgasmic Dysfunction 7,8 2% < 1%
1Adverse events for which the Effexor XR reporting rate was less than or equal to the placebo rate are not included. These events are: abdominal pain, abnormal vision, accidental injury, anxiety, back pain, diarrhea, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, nervousness, pain, paresthesia, pharyngitis, rash, rhinitis, and vomiting.
2 < 1% means greater than zero but less than 1%.
3Mostly “hot flushes.”
4Mostly “decreased appetite” and “loss of appetite.”
5Includes “delayed or retarded ejaculation” and “anorgasmia.”
6Percentage based on the number of males (Effexor XR = 335, placebo = 238).
7Includes “anorgasmia” and “delayed orgasm.”
8Percentage based on the number of females (Effexor XR = 666, placebo = 424).

Look at the Placebo Group
Now scroll down that page a bit until you find Table 3. The data here summarize reported side-effects for the three groups (Major Depressive Disorder, General Anxiety Disorder, and Social Anxiety Disorder) versus Placebo during the 8- to 12-week period the patients were actually taking the drug: This is probably more meaningful information for someone just beginning the medication.

Notice first that many of the listed side-effects are associated with numbers like 4 per cent, 3 per cent, 2 per cent, 1 per cent, or less than 1 per cent. That means that 96 per cent or more of the people taking this medication will not experience those symptoms, so they are not things you need worry greatly about.
Looking next at the bigger numbers, it seems that 31 per cent of people on Effexor complained of nausea. Two things to note about that: First, this means that almost 70 per cent did not experience this side effect so the odds are you may be one of the lucky ones; and, second, that 12 per cent of people in the placebo group also complained of nausea. The difference in this case (12 per cent vs. 31 per cent) is probably meaningful and I would probably consider this to be a significant side-effect for this medication. But it does raise the general question of whether a reported symptom is associated with the illness rather than the medication. A better example of this is seen a little further down the page: Some individuals taking Effexor complain of sleep disturbance. However, note that about equal numbers complain of somnolence (excessive sleepiness or drowsiness) and insomnia (17 per cent for each symptom). It is also noteworthy that for individuals taking the placebo 8 per cent complained of somnolence and 11 per cent complained of insomnia. Now, changes in sleep patterns are known symptoms of depression — there are suggestions in these data that Effexor may exacerbate that particular problem in some individuals but it is still worth noting that over 80 per cent of patients taking the drug do not report these side-effects.Then we come to a couple of side-effects that seem to be clearly caused by the medication: First, excessive sweating is reported by 14 per cent of patients taking Effexor but only 3 per cent of placebo patients. Second, abnormal (delayed) ejaculation in males is reported by 16 per cent taking the drug while less than 1 per cent of those in the placebo group complain of this side-effect. Again, it is worth noting that the vast majority (approximately 85 per cent) will not experience this side-effect but when it occurs it is probably safe to attribute it to the medication.

If you’re one of the unlucky ones…
Finally, with modern medications, there is now a considerable range of alternative medications to treat most illnesses. If you are experiencing one of the listed side-effects or even one that isn?t listed but that you think might be related to the medication, let your doctor know. In most cases, the problem can be solved by switching to one of the alternative drugs used to treat your condition.