Contrary to prevailing opinion, new research indicates it is not depression that
raises blood pressure but the drugs used to treat depression ¡X 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 ¡X not high ¡X 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 ¡X symptoms that may cause
depression, she said.

She added that the association may go both ways ¡X 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
¡X and the possible increased risk for hypertension."