Medications for clinical depression and anxiety

Diagnosing and treating clinical depression, also known as Major Depressive Disorder (MDD), involves a comprehensive evaluation since no single test definitively identifies it, and there are several options for treating people once a diagnosis has been reached. You can read about the general approach in our more detailed article here. The diagnosis process requires clinical judgment and expertise, and it is widely accepted that when treating clinical depression, the earlier the intervention, the better the outcomes typically are. CALL 988 LIFELINE FOR SUPPORT! If a person suspects they or someone they care about might be suffering from depression, it is essential to get professional help. This is especially important when a person harbors suicidal or self-harm thoughts. There has been a considerable increase in people asking for help because of their fears of self-harm. In July of 2022, the 10-digit National Suicide Prevention Lifeline transitioned to the easy-to-remember three-digit 988 Suicide & Crisis Lifeline, which operates 24/7, allowing people experiencing substance abuse, suicide, and/or mental health crises to connect with trained counselors. In the last year, the service has already answered more than 372,000 contacts (including calls, chats, and texts). That’s more than a 100% increase over an equivalent period on the old lifeline. If someone in your family suffers from depression (or other mental health disorders), you can contact your local NAMI (National Alliance for the Mentally Ill) for support and information about resources near you.

How is Major Depressive Disorder diagnosed?

Typically, a medical practitioner reaches a diagnosis through a detailed process that involves:

• In a clinical interview, a practitioner will ask about the patient’s symptoms, including duration, severity, and impact on daily functioning. The patient’s medical history, past mental health issues, family history of mental health problems, and any medications or treatments they’re currently receiving will be reviewed. The clinician may also enquire into other aspects of the patient’s life, such as relationships, work, and daily activities, to get a complete view of their situation.
• Conducting a physical examination to rule out other medical conditions that might be causing the symptoms. The doctor may order specific laboratory tests, such as blood tests, to check for abnormalities in thyroid function, vitamin deficiencies, or other potential causes or contributors to depressive symptoms.
• Gathering details about any medications the patient is taking, as some medicines can cause symptoms of depression, as well as discuss alcohol or recreational drug use.
• A psychological evaluation by a psychologist or psychiatrist may be suggested. These specialists can conduct a more in-depth assessment of the patient’s mood, thoughts, feelings, and behaviors.

The established manual for diagnosing MDD is the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). According to the DSM-5, to be diagnosed with MDD, symptoms must include at least five out of the following symptoms, and they must be present most of the day -nearly every day- for at least two weeks, must cause significant distress or impairment in daily living, and not be a result of substance abuse or another medical condition:

• Depressed mood
• Recurrent thoughts of death or suicide or a suicide attempt
• Loss of interest or pleasure in almost all activities
• A significant change in appetite
• Substantial weight loss or gain
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Indecisiveness
• Feelings of worthlessness or excessive guilt
• Diminished ability to think or concentrate

  Practitioners might use additional tools or questionnaires to support their diagnosis or to gauge the severity of depression, and it’s crucial to distinguish MDD from other mental health disorders and conditions that can mimic its symptoms, such as:

• Bipolar disorder
• Dysthymia (persistent depressive disorder)
• Adjustment disorders
• Medical conditions like hypothyroidism or vitamin deficiencies

What are the options for treating clinical depression?

Clinical depression, or major depressive disorder (MDD), can be treated using a combination of pharmacological, psychotherapeutic, and alternative approaches. Here is a summary of the spectrum of treatments:

• Pharmacological treatments. Most often, antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), antipsychotics, or mood stabilizers.
• Psychotherapeutic treatments, such as Cognitive Behavioral Therapy (CBT), Interpersonal Therapy (IPT), Psychodynamic Therapy, Dialectical Behavior Therapy (DBT), Problem-Solving Therapy
• Electroconvulsive Therapy (ECT)
• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Vagus Nerve Stimulation (VNS)
• Lifestyle modifications involving diet, avoiding alcohol and recreational drugs, and ensuring adequate sleep
• Alternative therapies, such as light therapy, meditation, and mindfulness, acupuncture, and biofeedback
• Support groups and peer support.

For those patients who are severely depressed or at risk of harming themselves or others, inpatient or outpatient day treatments might be necessary. Individuals must consult a healthcare provider to establish the most appropriate treatment based on their unique symptoms, severity, and overall health.

What are the likely chemical and metabolic causes of MDD?

A “chemical imbalance involving neurotransmitters” has become a common way of describing the underlying biology of depression and anxiety. However, neurotransmitters are just one part of a vast process of functions and structures that play a role in mood disorders. Serotonin, norepinephrine, and dopamine are the primary neurotransmitters that play some role in MDD. They are chemical messengers that transmit signals in the brain and play crucial roles in regulating mood, emotion, motivation, sleep, and many other functions. The relative aspects of the main neurotransmitters, especially about depression and anxiety, are:

Serotonin (5-hydroxytryptamine or 5-HT)

Often referred to as the “feel-good” neurotransmitter, it influences many body and psychological functions. It helps regulate mood, social behavior, appetite, digestion, sleep, memory, and sexual desire. Low levels of serotonin have been linked to mood disorders, especially depression. That’s why many antidepressants focus on increasing serotonin levels in the brain. Serotonin is also implicated in anxiety. It’s believed that an imbalance or inefficient functioning of serotonin pathways might contribute to heightened or prolonged anxiety states.

Norepinephrine (Noradrenaline)

Norepinephrine functions both as a neurotransmitter and a hormone. It plays its crucial role as the “fight or flight” trigger, preparing the body to react to a perceived threat. It increases alertness, arousal, speeds reaction time, and is involved in the brain’s reward system. Low levels of norepinephrine have been associated with fatigue, lack of motivation, and low mood, all symptoms commonly seen in depression. Conversely, high levels have been linked to anxiety, stress, and high blood pressure.

Dopamine

Dopamine is known as the “reward” neurotransmitter. It plays a central role in the brain’s reward and pleasure centers and is crucial for pleasure and motivation. Dopamine helps regulate movement and emotional response and enables a person to see rewards and take action to move toward them. Low dopamine levels can be a hallmark of certain types of depression (like atypical depression). It is often found in individuals with apathy, lack of interest in life, low motivation, and low mood. Some people with MDD may have decreased sensitivity to dopamine, leading to reduced feelings of pleasure or reward. Anxiety disorders are not directly tied to dopamine in the same way as depression is. Still, evidence suggests that dopamine dysregulation can contribute to symptoms in certain types of anxiety disorders. For example, medications that affect dopamine levels and signaling can impact anxiety symptoms.

What are the links between MDD and neurotransmitters?

The exact cause of depression and anxiety is multifactorial, involving genetic, biological, environmental, and psychological factors. Neurotransmitter imbalances are believed to be a foundation. Still, it’s essential to note that there is usually more than a “chemical imbalance” producing the overall condition that a person may be experiencing.

What medications can be prescribed for treating clinical depression, MDD, and anxiety?

While improving neurotransmitter levels and efficiency can help alleviate symptoms for many people, it’s not a one-size-fits-all solution. That’s why a comprehensive treatment approach often involves a combination of medication, therapy, lifestyle changes, and other interventions. Where medications are part of the treatment of clinical depression and anxiety, the  most frequently prescribed drug therapies are as follows:

Selective Serotonin Reuptake Inhibitors (SSRIs)

Examples: Prozac (fluoxetine), Celexa (citalopram), Paxil (paroxetine), Zoloft (sertraline) SSRIs work by increasing the levels of serotonin in the brain by blocking its reabsorption. They are considered safe, with fewer side effects than older antidepressants, and are effective for treating clinical depression as well as anxiety disorders. A main drawback can be a slightly increased risk of suicidal thoughts, especially in young adults and adolescents.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Examples: Cymbalta (duloxetine), Effexor (venlafaxine) SNRIs increase the levels of both serotonin and norepinephrine in the brain by blocking their reuptake. They are effective for major depression and certain anxiety disorders and may relieve pain in some individuals.

Benzodiazepines

Examples: Ativan (lorazepam ), Klonopin (clonazepam), Xanax (alprazolam) Benzodiazepines enhance the effect of gamma-aminobutyric acid (GABA). This neurotransmitter reduces activity levels in the brain, leading to sedative and anti-anxiety effects. These drugs provide fast-acting relief from acute anxiety. They can also be used as a muscle relaxant or to treat seizures. They may be contraindicated because of the risk of dependence and addiction, which makes them not ideal for long-term use.

Beta Blockers

Examples: Inderal (propranolol), Tenormin (atenolol) Beta-blockers block beta receptors of noradrenaline and adrenaline, which are produced naturally by the body as the “fight or flight” hormone. They are commonly used to lower blood pressure, as well as for reducing physical symptoms of anxiety. They can be prescribed off-label for performance anxiety.

Atypical antipsychotics

Examples: Seroquel (quetiapine), Abilify (aripiprazole), Zyprexa (olanzapine) Primarily used to treat schizophrenia, their exact mechanism for treating depression or anxiety is presumed to be related to inhibiting receptors on the dopamine (DA) pathway in the prefrontal cortex and blockage of the norepinephrine transporter (NET). Atypical antipsychotics can be effective when other treatments fail, especially in treatment-resistant depression.

Monoamine Oxidase Inhibitors (MAOIs)

Examples: Zebeta (bisoprolol fumarate) MAOIs block the enzyme monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine. It can be effective for treating clinical depression in some people who don’t respond to other treatments. Due to dietary actions and potential interactions with other drugs, they are not commonly prescribed.