Depression IV: Newer Pharmacotherapies for Depression

The traditional pharmacological methods of treating depression leave a lot to be desired.  The monoamine antidepressants, which include the first-line selective serotonin reuptake inhibitors (SSRI’s), end up working for just 70% of depressed patients. However only 50% respond on the first attempt.  For those not initially responding, dosage adjustments or perhaps switching to another antidepressant can sometimes help.  However a treatment can take about a month to determine effectiveness and if multiple attempts are necessary, even more time will be required.  Furthermore, even when “effective”, the therapeutic outcome can be less than desired.  Clearly we need quicker acting, more effective, first-line antidepressants  .

While the first-line SSRI’s have fewer side effects than the earlier generation antidepressants, side effects can still be significant.  Side effects can include headaches, nausea, trouble sleeping, dizziness, diarrhea, fatigue, anxiety, stomach upset, dry mouth, and sexual problems such as low sex drive, erectile dysfunction or ejaculation problems.  While these side effects often diminish over time, they nonetheless make compliance difficult for some patients.  Overdosing a patient can also cause serotonin syndrome (described in an earlier post under “SSRI side effects”)  which, in extreme cases, requires hospitalization.

Yet another problematic issue with monamine antidepressants is that when taken over an extended period, patients can develop pharmacological tolerance.  If a patient then discontinues treatment, unpleasant withdrawal symptoms can sometimes last a month or more (also referred to as antidepressant discontinuation syndrome).  Although withdrawal symptoms can be diminished by gradually tapering the drug and taking other medications to counteract withdrawal symptoms, some patients experience sufficiently unpleasant symptoms that they choose not to quit.

The 30% of patients who do not respond to 2 or more standard antidepressant treatments are termed “treatment resistant.”  There are “last-resort”, non-drug therapies that can help.  These treatments include electroconvulsive-shock therapy (ECT), repetitive transcranial magnetic stimulation, vagus nerve stimulation, and deep-brain stimulation.  Of these, ECT is the most used and most effective, and by some accounts, even more effective than traditional antidepressant drugs.  However, in addition to invasiveness, these treatments are expensive because they require hospital settings, specialized equipment, and a team of trained professionals.  For example, each ECT session costs about $2,500 and the typical 10 or so sessions over a period of several weeks would cost around $25,000, plus any additional costs of a hospital stay.  Depending upon one’s insurance, these costs may, or may not, be covered.  There are also no guarantees of lasting effects.

The good news is that we now have two classes of “antidepressant” psychedelic drugs that are both quicker and more effective than the monoamine antidepressants.  The bad news is that their high cost and limited availability puts them out of reach for many individuals.  The drugs themselves are not particularly expensive.  However,  like the non-drug therapies, the cost of treatment is.  Because of their federal classifications, these drugs must be administered under licensed medical supervision.  Self administration outside of medical settings, for either therapeutic or recreational purposes, is illegal.

One experimental class of psychedelics (including LSD, psilocybin, and ayahuasca) has limited availability for treating depression.  Because these drugs are not normally allowed for medical use, each therapist in the USA must obtain special FDA approval.  However, the other class (including ketamine and its derivatives) can more routinely be used “off label”.  Off label means that while the drug is available for medical use, the FDA has not given formal approval for its use as an antidepressant.  Because medical use is off label, insurance companies typically do not cover costs, which can run into thousands of dollars per month

There is hope that scientists can discover new drugs that retain the antidepressant effect of psychedelics without their acute psychoactive effects.  Unless that happens these psychedelics are likely to remain secondary antidepressants, used mainly for treatment-resistant patients as an alternative to the more invasive non-drug therapies. 

The remaining posts on depression explore the use of these psychedelics for treating depression.  However to provide background, other medical and recreational uses of these drugs are explored as well.
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