STUDY TO INVESTIGATE THE EFFECTS OF LEVOCETIRIZINE AND HYDROXYZINE ON COGNITIVE AND PSYCHOMOTOR FUNCTIONING DURING SIMULATED DIVING AT 2 BAR AND 4 BAR IN PROFESSIONAL NAVY DIVERS

Antihistamines are commonly used and currently levocetirizine is most
frequently prescribed in the Netherlands. They are commonly used by divers, to
solve ear, nose and throat problems, especially to open tubal passage. All
antihistamines cross the blood-brain barrier, where they block the
H1-receptors. First-generation antihistaminic drugs (like hydroxyzine) are
associated with sedation, CNS-depressant effects and an impairment of cognitive
and psychomotor functions. They bind non-selective to the H1-receptors in the
brain and interact with adrenergic, serotonergic and cholinergic neurons. This
causes sedative effects. Second-generation antihistamines have less lipophilic
properties than the first generation and bind more selective to the
H1-receptors. Third-generation antihistamines are supposed to have no unwanted
sedative effects.
While diving, increased pressure and different N2/O2 concentrations are known
to affect performance at a depth of 20 mt (3 bar) or deeper. This is caused by
nitrogen narcosis. Nitrogen narcosis is caused by competitive binding of
nitrogen to synapses of nerve ends in the body. This causes that
neurotransmitters cannot bind, which causes disturbance of the nerve system. As
a result, effects such as impaired neuromuscular coordination, slowed mental
activity, euphoric feelings and impaired memory, have influence on the
psychomotor and cognitive functions have been reported. Adverse effects of
psychoactive drugs can be additive or interact with the effects of diving.
Unfortunately, scientific research in this area is scarce. Therefore,
physicians are careful when prescribing medication to divers. The unknown
effects during increased pressure, different N2/O2 concentration, the uptake
and elimination of inert gas, and the risk that medication can act synergistic
on the sedative effects of nitrogen narcosis often make physicians to choose
(a) not to prescribe psychoactive medication, or (b) prohibit diving while
treated.
This study investigates the effects of antihistamines in hyperbaric conditions.

Investigate the effects of levocetirizine, hydroxyzine and placebo on cognitive
and psychomotor functioning during controlled simulated diving in a hyperbaric
chamber in professional navy divers at 10 mt (2 bar) and 30 mt (4 bar).

A double-blind, placebo-controlled crossover study.

Each subject performs 3 test days: levocetirizine (5 mg), hydroxyzine (50 mg)
and placebo.

The dive profile/procedure has the approval of the Surgeon General and the
Super Intendant of Diving of the Royal Netherlands Navy. The dive test is
within the normal safety limits and is not an exceptional exposure according
the RNLN Diving Manual. The dive profile fits within the regular training
capabilities of the participants.
The risks are minimal, because tests are performed in a diving simulator
supervised by medical and technical personnel. Subjects are professional Navy
divers. Dives are not known to produce serious adverse events. Adverse events
usually disappear within a couple of hours after intake of the drugs. There are
no specific benefits for participants, besides gaining insight in their own
diving performance. Military divers will receive reimbursements for the diving
according Navy regulations based on depth/time profile. They will recieve 120
euro for each simulated dive, 360 euro for the complete study.