618 CHAPTER 15
couple of MAOIs that do not require any dietary restrictions (Stahl, 2013). And while
these precautions are very important, certain drug–drug interactions may be more com-
mon and sometimes even lethal, so individuals taking MAOIs should work closely with
their health-care professionals to monitor adverse drug interactions (Julien et al., 2011;
Preston et al., 2008; Stahl, 2013).
The second category of antidepressant drug to be developed is called the tricy-
clic antidepressants. These drugs were discovered in the course of developing treatments
for schizophrenia (López-Muñoz & Alamo, 2009). Tricyclics, so called because of their
molecular structure consisting of three rings (cycles), increase the activity of serotonin
and norepinephrine in the nervous system by inhibiting their reuptake into the synap-
tic vesicles of the neurons. to Learning Objective 2.3. Some common tricyclics
are imipramine (Tofranil), desipramine (Norpramin, Pertofrane), amitriptyline (Elavil),
and doxepin (Sinequan, Adapin). Side effects of these drugs, which may also decrease
over the course of treatment, are very similar to those of the MAOIs but can also include
skin rashes, blurred vision, lowered blood pressure, and weight gain (Julien et al., 2011;
Preston et al., 2008; Stahl, 2013).
The effect of the MAOIs and the tricyclics on the action of the three critical neu-
rotransmitters led researchers to try to develop drugs that would more specifically tar-
get the critical neural activity involved in depression with fewer negative side effects.
This led to the development of the selective serotonin reuptake inhibitors (SSRIs), drugs that
inhibit the reuptake process of only serotonin. This causes fewer side effects while still
providing effective antidepressant action, making these drugs relatively safe when com-
pared to the older antidepressants. But like the other two classes of antidepressants, the
SSRIs may take from 2 to 6 weeks to produce effects. Some of the better-known SSRIs are
fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Other classes of antide-
pressants have been or are being investigated, including serotonin-norepinephrine reuptake
inhibitors (SNRIs), serotonin partial agonist/reuptake inhibitors (SPARIs), norepinephrine-
dopamine reuptake inhibitors (NDRIs), selective norepinephrine reuptake inhibitors (NRIs), and
serotonin antagonist/reuptake inhibitors (SARIs).
There is also research examining the potential use of subanesthetic doses of ket-
amine as an antidepressant due to its apparent ability to have immediate antidepressant
effects and reduction of suicidal thoughts (Stahl, 2013). The effects are not perma-
nent, but its effects can come on within a few hours and last for several days and up
to a week in some individuals (DiazGranados, Ibrahim, Brutsche, Ameli, et al., 2010;
DiazGranados, Ibrahim, Brutsche, Newberg, et al., 2010; Zarate et al., 2006; Zarate
et al., 2012). In addition to rapid effects, it appears to also facilitate synaptogenesis and
reverse some of the neuronal effects of chronic stress (Duman & Aghajanian, 2012).
Drugs that act like ketamine are being investigated for potential use as antidepressants.
Ketamine itself is an anesthetic, sometimes abused due to its dissociative and halluci-
nogenic effects (e.g., “Special K” or “K”), or used in cases of sexual assault.
Concerns have arisen that children and teenagers taking newer antidepressant
medications may have an increased risk of suicide versus those not receiving treatment.
Recent meta-analyses have provided conflicting information, with some data suggesting
an increased risk for suicide while other data do not support an increased risk (Gibbons
et al., 2012; Hetrick et al., 2012). Where there is an increased risk, it is possible depressive
symptoms are being addressed while suicidal thoughts and behavior are not reduced.
Regardless, caution is urged, especially in children and teens being treated with newer
antidepressant medications.
With regard to other uses for antidepressant medication, in the last several
years the use of the benzodiazepines to treat anxiety has declined, and physicians
and therapists have begun to prescribe antidepressant drugs to treat anxiety and
related disorders such as panic disorder, obsessive-compulsive disorder, and post
traumatic stress disorder. Although the antidepressants take from 3 to 5 weeks to
