Getting Properly Diagnosed & Additional Therapies for Treatment-Resistant Depression with Dr. Alison McInnes

By Ruika Lin

Earlier this month, I wrote my first guest blog post for 2-Minute Mind Check on Mindfulness-Based Cognitive Therapy with Dr. Stu Eisendrath, diving deep into MBCT’s structure, benefits, and positive results in tackling Treatment-Resistant Depression (TRD). Today’s post is going to cover the two sessions delivered by Dr. Alison McInnes during last month’s Not Your Mother’s Therapy event: the essentials of getting properly diagnosed for depression, and additional therapies for TRD.

The evening began with Dr. McInnes’ discussion on how to get properly diagnosed for depression. First of all, a psychiatrist will do a standard clinical interview which will include discovery about the patient’s chief complaint, history of the present illness and when the symptoms started, any hospitalizations or suicide attempts, a detailed medication history, and medical history. A psychiatrist will also conduct an assessment of the severity and chronicity of the patient’s symptoms. Dr. McInnes’ also mentioned that a good primary care doctor can also diagnose depression, but TRD is the type of depression where a psychiatrist comes in and can be the most helpful.

Depression is a mental health disorder that can have different symptoms depending on the person. For most people, depression changes how they function day-to-day, typically for more than two weeks. Depression can be defined as either having little interest or pleasure in doing things, or feeling down, depressed, or hopeless. Even though symptoms can vary based on the individual, common ones include changes in sleep (too much or too little), appetite, and movement (less active or more irritable), lack of concentration, loss of energy, low self-esteem, hopelessness or guilty thoughts, physical pains, and self-harm or suicidal thoughts. In particular, Dr. McInnes stressed that any level of suicidal thoughts and attempts must be taken very seriously. A critical method for recording patients’ symptoms is a Patient Health Questionnaire (PHQ) used by psychiatrists in estimating the severity of depression via a standardized scale. The questionnaire is especially useful before and after treatment in order to assess both its effectiveness and whether the patient’s symptoms have improved.

Other helpful information that a psychiatrist might need to make a proper diagnosis includes family psychiatric history with response to medications, the patient’s level of substance abuse, social history or a history of trauma, and mental status. When making a potential diagnosis for depression, psychiatrists record the patient’s appearance, motor movements, eye contact, orientation, speech, mood (how the patient states he/she feels), affect (how psychiatrist thinks the patient appears - it’s important to know whether affect is consistent with the mood), thought processes and content, perceptual disturbances, insight/judgment, memory and more. The results of mood surveys can help psychiatrists quantify response to treatment. Several lab tests such as TSH (thyroid function) and Vitamin D levels - especially in older patients - can also be helpful in the diagnosis.

Following Dr. Stu Eisendrath’s informative session on MBCT, Dr. McInnes returned to the topic of Treatment-Resistant Depression and discussed a number of additional therapies for this more common type of depression. Honing in on the neuroscience of depression, Dr. McInnes shared that traditional antidepressants target the three neurotransmitters that are collectively referred to as the biogenic amines: serotonin, norepinephrine, and dopamine. All traditional antidepressants, including Prozac, Zoloft, Lexapro, Wellbutrin, and more, are some combinations of these three neurotransmitters. They take about four to six weeks to work, and can be very effective, with common side effects such as decreased libido, emotional numbing, and weight gain. Antidepressants can be used to treat both depression and anxiety including OCD, PTSD, and Social Anxiety Disorder (SAD).

For TRD patients who do not respond to at least two additional antidepressants, alternative therapies such as Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT), and ketamine treatment can be helpful, as medications targeting the aforementioned neurotransmitters are not effective in 35-45% of patients. In addition, it’s also important to note that depression must be moderate to severe in nature to warrant these alternative therapies.

TMS is an FDA-approved treatment for TRD. The treatment involves sending magnetic pulses into areas of the brain that resets the brain’s neural circuitry to restore functional connectivity between brain regions implicated in mood disorder.  TMS treatment is structured as a 40-minute session per day for five days a week during a five-week period. Aside from headaches, TMS has minimal side effects.

ECT is another FDA-approved method for rapidly treating severe depression, having been gradually refined over the years to be more effective with fewer side-effects. Similar to ketamine, ECT addresses suicidal ideation. But unlike ketamine, ECT can also treat psychotic depression. With ECT, electrodes are placed on the patient’s scape and a finely controlled electric current is applied while the patient is under general anesthesia, causing a brief seizure in the brain. Common side effects of ECT include short-term memory loss and complications of anesthesia, but patients can become remarkably better very fast, with about eight sessions needed in general.

Emily Hine (Moderator), Dr. Alison McInnes, Dr. Stu Eisendrath  Not Your Mother’s Therapy - audience Q & A

Emily Hine (Moderator), Dr. Alison McInnes, Dr. Stu Eisendrath

Not Your Mother’s Therapy - audience Q & A

As for ketamine, Dr. McInnes devoted the rest of the evening diving deep into this particular treatment that targets a new class of neurotransmitters. Invented by Parke-Davis in 1962 as an anesthetic alternative to Phencyclidine (PCP), ketamine was widely popularized during the Vietnam War as a surgical anesthesia used among soldiers. In the 1970’s, ketamine was used to treat alcohol addiction in Russia. But in the 1990’s, ketamine’s remarkable and fast antidepressant response was discovered. Over the last few years, communities of patients who’ve received ketamine treatment strongly advocated for its wider accessibility, thanks to its effectiveness. As a result, in 2017, the APA issued a consensus statement on how to safely administer ketamine intravenously for depression.

Ketamine is an NMDA-receptor antagonist that acts on the glutamate neurotransmitter system which is different from the biogenic amines. As it can be a drug of abuse (though with weak addiction liability), and as there has been a lack of long-term safety data for repeated used, ketamine has yet to be paid for by insurance companies. However, given the lack of alternatives and advocacy from the community, psychiatrists have taken the initiative and treated patients in need.

Ketamine works by promoting neuroplasticity,  the formation of synapses (connection between neurons), leading to an increase in the potential for learning after  treatment. Given this increase in learning potential, even if the patient has failed multiple trials of psychotherapy in the past or found them unhelpful, all patients are strongly encouraged to participate in intensive, skills-based psychotherapy (CBT/DBT) with their new level of possibility for learning. Thanks to the new learning ability, therapy can become deeply enriched as well. In fact, MBCT has been found independently to be the most effective type of therapy to pair with ketamine treatment. In preparation for a ketamine infusion, patients are advised to avoid any stress-provoking stimuli prior to the treatment, avoid alcohol consumption and stop any benzodiazepines intake to maximize response of ketamine treatment.

Currently the way to access generic ketamine is through practitioners who administer it intravenously, intramuscularly, or provide an oral version. In 2019, an intranasal form of ketamine, Esketamine, will be FDA approved and marketed for use by the pharmaceutical company Janssen.

Candidates for Ketamine Therapy can be from all age ranges. Bipolar patients in a current depressive episode can also be treated, given that they have adequate mood stabilization and are not using any substances. PTSD, Generalized Anxiety Disorder (GAD), OCD, and SAD are also treatable with ketamine. A few exclusions include patients with active substance abuse, history of psychosis, history of increased intracranial pressure, pregnancy, uncontrolled hypertension, and previous negative response to ketamine.

Towards the end, Dr. McInnes also addressed a few psychedelics-based treatment in development, including the highly-structured nine-hour MDMA treatment sessions targeting PTSD, psilocybin for depression, and LSD for depression, the latter two both in very early stages of development. Dr. McInnes cautioned against microdosing on one’s own because exact dosing is important and because she believes psychedelics should be taken under the supervision of a therapist.  New treatments are constantly being developed and as an example, Dr. McInnes wrapped up her second talk with an incredibly sweet story of a therapy piglet helping with work stress on the East Coast, leaving me with a heartfelt smile on my face at the end of a highly-informative event.

Thanks to Emily Hine for moderating this discussion, to WeWork for hosting us, and to the 2-Minute Mind Check (2MMC) for organizing this informative conversation, Not Your Mother’s Therapy. As a San Francisco Bay Area community initiative aimed at helping employees in the Bay Area determine where they stand on the depression scale, 2MMC is a great place to find resources for you or your loved ones who are suffering. Don’t forget that you can check out more helpful blogs, as well as free depression tools and resources at 2-Minute Mind Check.

About the author:



Born and raised in Sichuan, China, I’m a San Francisco-based bilingual content marketer, musician, and writer. Immensely curious about the human minds, I write about psychology and emotions, culture clashes, and music. Read my articles here, and connect with me on LinkedIn here.