Depression Lowers Blood Pressure, but Antidepressants Increase It
Tricyclics Could Be a Cause
Pauline Anderson
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March 3, 2009 — Contrary to prevailing opinion, new research indicates it is not depression that raises blood pressure but the drugs used to treat depression — a
finding that suggests patients on antidepressants might need to be more closely monitored.
Investigators at the VU University Medical Center, in Amsterdam, the Netherlands, show that depression is associated with low — not high — blood pressure but that
taking certain antidepressants, particularly tricyclic antidepressants (TCAs), tends to raise blood pressure and increase the risk for hypertension.
"Doctors should at least be aware of a potential blood-pressure rise that could be linked to TCA use, especially for patients with cardiovascular disease or high blood pressure or
others who are at risk for hypertension," lead author Carmilla Licht, from the department of psychiatry at VU University Medical Center, told Medscape Psychiatry.
"They may consider meticulously monitoring these patients' blood pressure when they prescribe 1 of these antidepressants or consider prescribing another antidepressant
medication."
The study is published online February 23 in Hypertension.
Contradicts Depression/Hypertension Theory
The study seems to contradict the theory that people with depression are more vulnerable to cardiovascular problems because their depression raises their risk for
hypertension.
"We showed that depression itself was not associated with high blood pressure and hypertension, so the hypothesis does not seem to hold," said Licht, who is preparing her doctoral
dissertation on the role of the autonomic nervous system in the relationship between depression (and anxiety) and cardiovascular diseases.
While the study found an association between low blood pressure and depression, it found a link between high blood pressure and anxiety.
Subjects for the study were part of the Netherlands Study of Depression and Anxiety, an ongoing analysis of 2981 adults aged 18 to 65 years. From this sample, 2618 subjects were
included in the current study.
Participants were divided into 3 groups: a control group with no history of anxiety or depressive disorder (590); patients with a major depressive disorder (MDD) or an anxiety
disorder who did not take antidepressants (1348); and patients with an MDD or an anxiety disorder who were on antidepressant medication. The researchers also differentiated between subjects with a
remitted MDD or anxiety disorder and those with a current diagnosis.
In the group using antidepressants, researchers determined the number of patients taking the various drugs: 442 used selective serotonin-reuptake inhibitors (SSRIs); 67 used a
TCA; and 135 used an antidepressant that works on noradrenergic and serotonergic (NS) systems.
To assess blood pressure, investigators averaged systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements taken twice during supine rest and adjusted these
readings for use of hypertension medications.
They then created a 5-category hypertension indicator:
- No hypertension (63.7% of study sample).
- Isolated systolic hypertension (15.8%).
- Isolated diastolic hypertension (2.7%).
- Hypertension stage 1 (defined as SBP greater than or equal to 140 and DBP greater than or equal to 90) (13.1%).
- Hypertension stage 2 (SBP greater than or equal to 160 and DBP greater than or equal to 100) (4.7%).
There was no difference in use of antihypertensives between the 3 groups.
No Association With SSRIs
Investigators also measured heart rate and respiratory sinus arrhythmia (RSA) and collected information on body-mass index and other variables including age, sex, and education.
Compared with controls, subjects with a psychiatric disorder were a little older, more likely to be female, less educated, less physically active, smoked more, and had a higher body-mass index and
more diseases.
Compared with healthy controls, patients with an MDD had a significantly lower mean SBP (remitted diagnosis: P = 0.02; current diagnosis: P = 0.002) and were less
likely to have isolated systolic hypertension. Both remitted and current MDD was associated with lower SBP even after researchers corrected for antidepressant use, RSA, and heart rate.
Patients taking a TCA had up to a 9% higher mean SBP and an 11% higher mean DBP compared with healthy controls and nonmedicated patients. And they had about double the risk of
having hypertension stage 1 and almost triple the risk of having hypertension stage 2.
The association between raised blood pressure and NS-working antidepressants was similar but weaker than that between TCAs and increased blood pressure. The use of SSRIs was not
significantly associated with increased blood pressure or hypertension.
Does Low BP Cause Depression?
On the other hand, patients with anxiety had a significantly higher mean DBP than controls (P = 0.03), although this did not significantly raise the risk for isolated
diastolic hypertension. These results remained after subjects using hypertension medication were excluded.
The study authors speculate on several possible reasons that depressed patients have low blood pressure. First, these patients may be more likely to use medications that treat
hypertension, although this study did not find more users of these drugs in the groups with a psychiatric diagnosis, and results were similar when antihypertensive users were excluded from the
analyses.
Another explanation could be that both depression and low blood pressure have a common cause. For example, a malfunction in metabolism that increases or decreases levels of
certain metabolites, hormones, or neurotransmitters may affect both depression and blood pressure, said Ms. Licht.
Perhaps the most likely explanation is that low blood pressure may actually cause depression. People with low blood pressure are often tired, cold, and dizzy and have problems
with concentration — symptoms that may cause depression, she said.
She added that the association may go both ways — individuals with low blood pressure may be more likely to become depressed, and those with depression may be more likely to
develop low blood pressure.
Some previous research is not in agreement with these results. In fact, some studies found a positive association between depression and high blood pressure. But Ms. Licht
believes the large sample size of the current study added weight to her results, as did taking into account the use of antidepressants.
In addition, she pointed out that while other studies focused on reports of depressive symptoms, this study included patients whose psychiatric diagnosis fulfilled Diagnostic
and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) criteria.
High BP Linked to Anxiety
As for the finding that anxiety is linked to high blood pressure, this might be due to the continuous stress experienced by people with anxiety. In such a state, the autonomic
nervous system becomes dysfunctional, explained Ms. Licht.
"The sympathetic "fight, flight, and fright" response increases, and that raises the heart rate, while the parasympathetic 'rest and digest' response decreases, and that lowers
heart-rate variability," she said, adding that both responses can influence blood pressure.
Why anxiety is associated only with DBP (and not SBP) is unclear, but might be related to the balance between sympathetic overactivity and parasympathetic underactivity in anxious
people, said Ms. Licht.
It is too soon to say emphatically that TCAs actually cause hypertension and that these drugs should not be prescribed, Ms. Licht said. However, she said that there is enough
research that strongly suggests TCAs and, to a lesser extent, NS-working drugs do play an important role in hypertension and dysregulation of the autonomic nervous system in depressed
people.
"Doctors should clearly consider whether the beneficial effects of antidepressants on depression outweigh the effect of increasing blood pressure — and the possible
increased risk for hypertension."
The authors report no disclosures.
Hypertension. Published online February 23, 2009
