About 20% of visits to health care providers involve difficulties with anxiety and depression and their various manifestations: Bipolar disorder as well as anxiety- and depression-spectrum disorders. These include generalized anxiety disorder (GAD) and major depressive disorder (MDD). Since anxiety and depression are related, you get mixed anxiety depression (MAD) and its lesser form, “anxious dysthymia,” since more milder forms of depression are called dysthymia. In addition, you have panic disorder, which is related to anxiety–they often co-occur–and the resulting spectrum of disorders are called anxiety or depression spectrum disorders.
What are the putative biological origins of anxiety and depression?
Let’s count the number of ways that anxiety and depression have been theorized to arise. Here are some of the major ones: The monoamine hypothesis, the neurotransmitter receptor hypothesis that posits the occurrence of abnormal receptors in the brain or aberrant signal transduction, insufficient genetic expression of relevant brain neurons, and the neurokinin hypothesis of emotional dysfunction.
The basis of the monamine hypothesis is that there is insufficient serotonin in the brain in individuals with anxiety and depression and females, on average, have about 1/3 less than males, leading to about a 2:1 ratio of female:male depressives or anxious individuals. In the case of the neurotransmitter receptor hypothesis, the lack of serotonin affects the receptors on neighboring neurons or the ability to transduce signals to neighboring neurons leading to anxiety and depression. The monoamine hypothesis of gene expression argues that the gene for brain-derived neurotrophic factor is repressed under stress undermining the viability of brain neurons, atrophy, apoptosis),
The neurokinin hypothesis of emotional dysfunction claims that the neurokinins in the brain, such as substance P, are causing anxiety and depression and by decreasing the availability of neurokinins, the regulation of emotions by individuals may be improved.
When the predominant symptoms are anxiety, it has been suggested that there is an overproduction of norepinephrine in the locus coeruleus deep within the subcortex of the brain and by blocking receptors on the surface of neurons that are sensitive to noreprinephrine, anxiety is reduced.
When the predominant symptoms are panic disorder, it has been posited that overproduction of norepinephrine in the locus coerleus is, rather, a result of abnormal discharge of norepinephrine neurons suggesting that panic attacks are similar to seizure-like activity in the areas of the brain that subserve emotions.
Post-traumatic stress disorder may also be due to overproduction of noreprinephrine in the locus coerleus but with accompanying arousal of the autonomic nervous system, an abnormal stress response, and an inflated startle response.
Cognitive-behavioral therapy (CBT) is effective for anxiety, depression, and panic disorder but in more moderate to severe cases, the addition of anxiolytic or anti-depressive medication may be more effective than CBT or medication alone. In very severe cases of depression and bipolar disorder–the occurrence of both depression and mania–electroconvulsive shock therapy (ECT) is still widely practiced in the psychiatric profession.
What about medication for anxiety and depression? The response rate for anti-depressant medication is only about 67% whereas the response rate for a placebo is around 33% suggesting that antidepressant medication is often not effective alone. For instance, when individuals who responded positively to a placebo are given an antidepressant, there is a 50% relapse rate while the rate of relapse is only 10% without a placebo. However, often many medications must be tried before the right one or more is found and then a “cocktail” of various psychoactive medications may be employed to get a favorable therapeutic dosage.
For instance, lithium is often prescribed for severe depression. Anticonvulsants (e.g., carbamazepine, galapentin, lamotrigine, and topiramate, and valproic acid), benzodiazipines such as diazepam and fluzazepam, which facilitate the production of gamma amino butyric acid or “GABA” that inhibits activity of the amygdala (one of the emotional centers of the brain), and atypical antipsychotics (i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone) are often used to stabilize mood and reduce manic symptoms. The benzodiazipine, Alprazolam, is often used to treat panic disorder. Estrogen supplements and stimulants such as dextroamphetamine are also sometimes used. Beta adrenergic blockers or psychoactive drugs that block epinephrine, another important neurotransmitter, and Paxil, a selective serotonin reuptake inhibitor, are often used to treat social phobias such as fear of public speaking.
What are some of the other medications used to treat anxiety and depression spectrum disorders?
Remeron (mirtazapine) and Serzone (nefazodone) are often prescribed for GAD and Effexor (Venlafaxine XR) to stabilize mood. Monoamine oxidase (MAO) inhibitors such as Aurorix, Marplan, Nardil, Parnate, and Selegiline are often effective in preventing the decay of another important neurotransmitter in the brain linked to depression, noreprinephrine. By inhibiting MAO, more noreprinephrine is made available to brain systems.
Tricyclic antidepressants such as Anafranil, Asendin, Elavil, Ludiomil, Norpramin, Parmelor, Sinequan, Surmontil, Tofranil, and Vivactil impede the reuptake of noreprinephrine and serotonin in the nerve synapse increasing the availability of these two neurotransmitters to brain systems.
The most common antidepressants and anxiolytics are selective serotonin reuptake inhibitors such as Celexa, Luvox, Paxil, Prozac, and Zoloft. They make more serotonin available to brain systems by preventing its “reuptake” in the nerve synapse. They are the treatment of choice in treating post-traumatic stress disorder.
There are also selective noradrenergic reuptake inhibitors such as reboxetine, noreprinephrine and dopamine reuptake inhibitors such as bupropion, serotonin-norepinephrine reuptake inhibitors such as venlafaxine and Effexor, alpha 2 antagonists or noradrenergic and specific serotonergic antidepressants such as mirtazapine, which increases the availability of serotonin and norepinephrine to brain systems, and serotonin 2A antagonist/reuptake inhibitors such as nefazodone and trazodone.
“Buspar” (buspirone) is a partial (serotonin) agonist and is often used to treat anxiety.
Anxiety spectrum disorders (GAD) are also treated with sedating antihistamines; beta adrenergic blockers; alpha 2 agonists such as clonidine; non-benzodiazepine short-acting hypnotics such as zalepon, zolpidem, and zopiclone; sedating antidepressants such as mirtazapine, nefazodone, and trazodone; sedating antihistamines such as diphenhydramine, doxylamine, and hydroxyzine; sedating anticholinergics such as scopolamine; and sedative-hypnotics such as choral hydrate, melatonin, and valerian. The latter two are available through your local health food store.
In all, quite a wide range of possible biological solutions.
Some suggested reading:
Beck, J. S. (1995). Cognitive therapy: Basics and beyond. NY: Guilford.
Stahl, S. M. (2000). Essential psychopharmacology: Neuroscientific basis and practical applications (2nd. ed.). Cambridge: University of Cambridge Press.